Radiogenomic biomarkers for immunotherapy in glioblastoma: A systematic review of magnetic resonance imaging studies.

Background: Immunotherapy is an effective "precision medicine" treatment for several cancers. Imaging signatures of the underlying genome (radiogenomics) in glioblastoma patients may serve as preoperative biomarkers of the tumor-host immune apparatus. Validated biomarkers would have the potential to stratify patients during immunotherapy clinical trials, and if trials are beneficial, facilitate personalized neo-adjuvant treatment. The increased use of whole genome sequencing data, and the advances in bioinformatics and machine learning make such developments plausible. We performed a systematic review to determine the extent of development and validation of immune-related radiogenomic biomarkers for glioblastoma. Methods: A systematic review was performed following PRISMA guidelines using the PubMed, Medline, and Embase databases. Qualitative analysis was performed by incorporating the QUADAS 2 tool and CLAIM checklist. PROSPERO registered: CRD42022340968. Extracted data were insufficiently homogenous to perform a meta-analysis. Results: Nine studies, all retrospective, were included. Biomarkers extracted from magnetic resonance imaging volumes of interest included apparent diffusion coefficient values, relative cerebral blood volume values, and image-derived features. These biomarkers correlated with genomic markers from tumor cells or immune cells or with patient survival. The majority of studies had a high risk of bias and applicability concerns regarding the index test performed. Conclusions: Radiogenomic immune biomarkers have the potential to provide early treatment options to patients with glioblastoma. Targeted immunotherapy, stratified by these biomarkers, has the potential to allow individualized neo-adjuvant precision treatment options in clinical trials. However, there are no prospective studies validating these biomarkers, and interpretation is limited due to study bias with little evidence of generalizability.

Post-craniotomy coronal suture diastases in a transformed lower grade glioma.

Cranial suture diastases are an uncommon clinical entity, with post craniotomy diastases being a previously undescribed finding in literature to our best knowledge. Herein, we report a case of a 28-year-old adult who underwent a second-stage low-grade glioma surgery 7 months after initial surgery. This study presents coronal suture diastases adjacent to the previously performed craniotomy. After literature and pathophysiology review, we found it to be unique and that the craniotomy can resemble the mechanical stress of trauma.

Cortical resting motor threshold difference in asleep-awake craniotomy for motor eloquent gliomas: WHO grading influences motor pathway excitability.

Developing neurophysiological tools to predict WHO tumor grade can empower the treating teams for a better surgical decision-making process. A total of 38 patients with supratentorial diffuse gliomas underwent an asleep-awake-sedated craniotomies for tumor removal with intraoperative neuromonitoring. The resting motor threshold was calculated for different train stimulation paradigms during awake and asleep phases. Receiver operating characteristic analysis and Bayesian regression models were performed to analyze the prediction of tumor grading based on the resting motor threshold differences. Significant positive spearman correlations were observed between resting motor threshold excitability difference and WHO tumor grade for train stimulation paradigms of 5 (R = 0.54, P = 0.00063), 4 (R = 0.49, P = 0.002), 3 (R = 0.51, P = 0.001), and 2 pulses (R = 0.54, P = 0.0007). Kruskal-Wallis analysis of the median revealed a positive significant difference between the median of excitability difference and WHO tumor grade in all paradigms. Receiver operating characteristic analysis showed 3 mA difference as the best predictor of high-grade glioma across different patterns of motor pathway stimulation. Bayesian regression found that an excitability difference above 3 mA would indicate a 75.8% probability of a glioma being high grade. Our results suggest that cortical motor excitability difference between the asleep and awake phases in glioma surgery could correlate with tumor grade.

Intraoperative Neuromonitoring of the Visual Pathway in Asleep Neuro-Oncology Surgery.

Brain tumour surgery in visual eloquent areas poses significant challenges to neurosurgeons and has reported inconsistent results. This is a single-centre prospective cohort study of patients admitted for asleep surgery of intra-axial lesions in visual eloquent areas. Demographic and clinical information, data from tractography and visual evoked potentials (VEPs) monitoring were recorded and correlated with visual outcomes. Thirty-nine patients were included (20 females, 19 males; mean age 52.51 ± 14.08 years). Diffuse intrinsic glioma was noted in 61.54% of patients. There was even distribution between the temporal, occipital and parietal lobes, while 55.26% were right hemispheric lesions. Postoperatively, 74.4% remained stable in terms of visual function, 23.1% deteriorated and 2.6% improved. The tumour infiltration of the optic radiation on tractography was significantly related to the visual field deficit after surgery (p = 0.016). Higher N75 (p = 0.036) and P100 (p = 0.023) amplitudes at closure on direct cortical VEP recordings were associated with no new postoperative visual deficit. A threshold of 40% deterioration of the N75 (p = 0.035) and P100 (p = 0.020) amplitudes correlated with a risk of visual field deterioration. To conclude, direct cortical VEP recordings demonstrated a strong correlation with visual outcomes, contrary to transcranial recordings. Invasion of the optic radiation is related to worse visual field outcomes.

Inter-dural spinal cyst with acute thoracic compressive myelopathy: anatomical aspects of spinal dura, case report and literature review.

INTRODUCTION: Inter-dural juxta-facet spinal cysts occur rarely. They form as part of the degenerative spinal disease process and can be misdiagnosed as synovial cysts or ganglion cysts. We report the case of a thoracic inter-dural juxta-facet spinal cyst causing acute compressive thoracic myelopathy. METHODS: The data was collected retrospectively from patient records. The literature review was performed in PubMed. RESULTS: We report a case of symptomatic inter-dural juxta-facet thoracic spinal cyst. The literature review showed a variety of different spinal cysts including arachnoid cyst, discal cyst, ganglion cyst, epidermoid cyst and synovial cysts. Micro-instability and repeated microtrauma associated with degenerative changes are most likely contributors to its formation. Asymptomatic cysts can show spontaneous resolution. When symptomatic, they can be managed with surgical excision with good patient outcome. CONCLUSION: Inter-dural spinal cysts can be diagnosed and surgically excised to produce excellent post-operative outcome. High pre-operative index of suspicion of this diagnosis together with good understanding of the intraoperative anatomy are essential to avoid inadvertent dural breach.

Therapeutic Strategies and Challenges in the Management of Craniospinal Tumors in Pregnancy: A Ten-Year Retrospective Tertiary-Center Study, Systematic Review, and Proposal of Treatment Algorithms.

OBJECTIVE: This study aims to review therapeutic strategies in the management of craniospinal tumors in pregnant patients and the factors that may influence the management along with their influence on maternal and fetal outcomes. METHODS: A retrospective single-center cohort study was performed at a tertiary neurosurgical referral center. Pregnant patients referred to the neuro-oncology multidisciplinary meeting (MDM) with craniospinal tumor were included. Ten-year patient data were collected from hospital records and neuro-oncology MDM outcomes. A systematic review was performed of the available literature as per PRISMA guidelines. RESULTS: Twenty-five patients were identified, with a mean age of 31 years. Of these patients, 88% (n = 22) had cranial lesions and 12% (n = 3) had spinal lesions. Most of the patients had World Health Organization grade I/II tumors. Of the patients, 44% underwent surgery when pregnant, whereas in 40%, this was deferred until after the due date. Of patients, 16% did not require surgical intervention and were followed up with serial imaging in the MDM. The left lateral/park bench position was the preferred position for the spinal and posterior fossa lesions. Systematic review and retrospective data led to proposal of treatment algorithms addressing the therapeutic strategy for management of craniospinal tumors during pregnancy. Factors that may influence maternal and fetal outcomes during management of these tumors were identified, including aggressiveness of the tumor and stage of pregnancy. CONCLUSIONS: Craniospinal tumors presenting in pregnancy are challenging. The surgical management needs to be tailored individually and as part of a multidisciplinary team approach. Factors influencing maternal and fetal outcomes are to be considered during management and patient counseling.

Mesenteric Ischemia and Its Need for Timely Recognition and Management.

Mesenteric ischemia is a fatal vascular emergency of the small intestine which, if not diagnosed and treated in time, has a very high mortality rate. Presenting with nonspecific symptoms such as abdominal pain, nausea, constipation, tachycardia, and gastrointestinal bleeds, it can masquerade as other causes of acute abdomen, particularly bowel obstruction. Ideal laboratory tests and markers are still lacking due to complexity in bowel's anatomy, physiology, blood supply, and drainage. We report 10 cases of mesenteric ischemia presented in our center with their demography, laboratory findings, approach to diagnosis, and treatment along with their outcomes at discharge. Out of the ten cases, six cases presented with signs and symptoms of acute bowel obstruction without passage of stool and one with passage of black stool. These seven patients underwent laparotomy, while the remaining three cases who either presented with milder symptoms or refused surgical interventions were managed conservatively. All patients were diagnosed with either acute or chronic mesenteric ischemia based on their operative and/or radiographic findings.

TEleRehabilitation Nepal (TERN) for People With Spinal Cord Injury and Acquired Brain Injury: A Feasibility Study.

BACKGROUND: Spinal Cord Injury (SCI) or Acquired Brain Injury (ABI) leads to disability, unemployment, loss of income, decreased quality of life and increased mortality. The impact is worse in Low-and Middle-Income Countries (LMICs) due to a lack of efficient long-term rehabilitative care. This study aims to explore the feasibility and acceptability of a telerehabilitation programme in Nepal. METHODS: Prospective cohort feasibility study in a community setting following discharge from a specialist rehabilitation centre in Nepal. Patients with SCI or ABI who had previously accessed specialist rehabilitation were connected to a specialist Multidisciplinary Team (MDT) in the centre through a video conference system for comprehensive remote assessments and virtual individualised interventions. Data were captured on recruitment, non-participation rates, retention, acceptability (via end-of-study in-depth interviews with a subset of participants) and outcome measures including the Modified Barthel Index (MBI), Depression Anxiety Stress Scale (DASS) and EuroQol-5D (EQ-5D), completed pre- and post-programme. RESULTS: 97 participants with SCI (n = 82) or ABI (n = 15) discharged from the centre during an 18-month period were approached and enrolled on the study. The telerehabilitation programme facilitated the delivery of support around multiple aspects of rehabilitation care, such as spasticity treatments and pain management. Outcome measures indicated a significant improvement in functional independence (P < .001), depression, anxiety and stress (P < .001) and quality of life (P < .001). Qualitative interviews (n = 18) revealed participants found the programme acceptable, valuing regular contact and input from MDT professionals and avoiding expensive and lengthy travel. CONCLUSION: This is the first study in Nepal to identify telerehabilitation as a feasible and acceptable approach to augment the provision of specialist rehabilitation. Future research is needed to assess the suitability of the programme for other conditions requiring specialist rehabilitation and determine the mechanisms underpinning improved outcomes for people with SCI or ABI. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04914650.

Combined extradural and intradural approach to a trigeminal nerve hemangiopericytoma with cranial nerve monitoring: a technical note of a rare case.

Hemangiopericytoma (HPC) of the trigeminal nerve is extremely rare. We present a case of a large cystic HPC of the mandibular division of the trigeminal nerve, only the third case described in the literature, with both intradural and extradural components. We describe the surgical approach, assisted by neurophysiological techniques of mapping and monitoring including blink reflex and triggered electromyography. Additionally, we report a method of monitoring of the sensory branches of the trigeminal nerve, poorly described in the literature, through peripheral and direct nerve stimulation and recording of transcranial somatosensory evoked potentials.

Simultaneous Motor and Visual Intraoperative Neuromonitoring in Asleep Parietal Lobe Surgery: Dual Strip Technique.

Background: The role played by the non-dominant parietal lobe in motor cognition, attention and spatial awareness networks has potentiated the use of awake surgery. When this is not feasible, asleep monitoring and mapping techniques should be used to achieve an onco-functional balance. Objective: This study aims to assess the feasibility of a dual-strip method to obtain direct cortical stimulation for continuous real-time cortical monitoring and subcortical mapping of motor and visual pathways simultaneously in parietal lobe tumour surgery. Methods: Single-centre prospective study between 19 May−20 November of patients with intrinsic non-dominant parietal-lobe tumours. Two subdural strips were used to simultaneously map and monitor motor and visual pathways. Results: Fifteen patients were included. With regards to motor function, a large proportion of patients had abnormal interhemispheric resting motor threshold ratio (iRMTr) (71.4%), abnormal Cortical Excitability Score (CES) (85.7%), close distance to the corticospinal tract­Lesion-To-Tract Distance (LTD)­4.2 mm, Cavity-To-Tract Distance (CTD)­7 mm and intraoperative subcortical distance­6.4 mm. Concerning visual function, the LTD and CTD for optic radiations (OR) were 0.5 mm and 3.4 mm, respectively; the mean intensity for positive subcortical stimulation of OR was 12 mA ± 2.3 mA and 5/6 patients with deterioration of VEPs > 50% had persistent hemianopia and transgression of ORs. Twelve patients remained stable, one patient had a de-novo transitory hemiparesis, and two showed improvements in motor symptoms. A higher iRMTr for lower limbs was related with a worse motor outcome (p = 0.013) and a longer CTD to OR was directly related with a better visual outcome (p = 0.041). At 2 weeks after hospital discharge, all patients were ambulatory at home, and all proceeded to have oncological treatment. Conclusion: We propose motor and visual function boundaries for asleep surgery of intrinsic non-dominant parietal tumours. Pre-operative abnormal cortical excitability of the motor cortex, deterioration of the VEP recordings and CTD < 2 mm from the OR were related to poorer outcomes.

First Human In Vivo Neuroelectrophysiology Recordings of Uncrossed Dentatothalamocortical White-Matter Connections: On the Fast Tract.

OBJECTIVES: We aim to demonstrate intraoperative recording of cerebellar to cortical pathways that have not been previously recorded in humans, though imaged. METHODS: We report 2 cases with intraoperative neurophysiologic mapping of cerebellocortical tracts. Direct electrical stimulation of subcortical cerebellum along with recordings of cortical evoked potential and motor muscle recordings was performed during surgery. MR tractography data from healthy participants were used to further illustrate the pathways. RESULTS: Neurophysiologic recordings showed large waveforms of evoked potentials in bilateral electrodes over premotor/motor cortices on stimulation of the dentate nucleus. EMG recordings showed responses in face and neck muscles on stimulation of the dentate nucleus at the motor threshold. We thus demonstrated first-in-human in vivo neurophysiologic evidence of cerebellum to cortex responses through an uncrossed dentatothalamocortical tract to the motor/premotor cortices. DISCUSSION: This technique provides a methodology for the direct mapping of the cerebellum and cerebello-cerebral connections. We hypothesize a direct structural connection from the dentate nucleus to the premotor and motor cortices, as well as to ipsilateral hemibody muscles, acting as a fast route of cerebellar output and back up for immediate motor responses. This will further help explain the modulatory effects of the cerebellum on motor, language, and cognitive functions.

Do All Notochordal Lesions Require Proton Beam Radiotherapy? A Proposed Reclassification of Ecchordosis Physaliphora as Benign Notochord Cell Tumor.

Objectives Ecchordosis physaliphora (EP) is a benign notochord lesion of the clivus arising from the same cell line as chordoma, its malignant counterpart. Although usually asymptomatic, it can cause spontaneous cerebrospinal fluid (CSF) rhinorrhea. Benign notochordal cell tumor (BNCT) is considered another indolent, benign variant of chordoma. Although aggressive forms of chordoma require maximal safe resection followed by proton beam radiotherapy, BNCT and EP can be managed with close imaging surveillance without resection or radiotherapy. However, while BNCT and EP can be distinguished from more aggressive forms of chordoma, differentiating the two is challenging as they are radiologically and histopathologically identical. This case series aims to characterize the clinicopathological features of EP and to propose classifying EP and BNCT together for the purposes of clinical management. Design Case series. Setting Tertiary referral center, United Kingdom. Participants Patients with suspected EP from 2015 to 2019. Main Outcome Measures Diagnosis of EP. Results Seven patients with radiological suspicion of EP were identified. Five presented with CSF rhinorrhea and two were asymptomatic. Magnetic resonance imaging features consistently showed T1-hypointense, T2-hyperintense nonenhancing lesions. Diagnosis was made on biopsy for patients requiring repair and radiologically where no surgery was indicated. The histological features of EP included physaliphorous cells of notochordal origin (positive epithelial membrane antigen, S100, CD10, and/or MNF116) without mitotic activity. Conclusion EP is indistinguishable from BNCT. Both demonstrate markers of notochord cell lines without malignant features. Their management is also identical. We therefore propose grouping EP with BNCT. Close imaging surveillance is required for both as progression to chordoma remains an unquantified risk.

Commissural Inter-M1 Cortico-cortical Evoked Potential: A Proof of Concept Report.

BACKGROUND: Intraoperative neuromonitoring of motor functions experienced a dramatical revolution in the last years thanks to significant advances in anesthesiology procedures and both preoperative and intraoperative mapping techniques. Asleep, awake, and combined intraoperative mapping techniques were responsible for an improvement in the functional outcomes in neurosurgery, providing reliable and reproducible mapping of both projection and association fibers involved in motor control. METHODS: We report inter-M1 cortico-cortical evoked potential (CCEP) recording during asleep resection of a bilateral parasagittal meningioma with intraoperative neuromonitoring and motor mapping. RESULTS: CCEPs were recorded between both M1 cortices with bipolar stimulations of both supplementary motor areas (10.5-11.5 µV). CONCLUSIONS: Here, we provide evidence of intraoperative mapping of commissural fibres involved in motor control in a patient with asleep technique as well as a review of the potential tracts involved in the connectivity underlying the motor function.

Steroid in Chronic Subdural Hematoma: An Updated Systematic Review and Meta-Analysis Post DEX-CSDH Trial.

BACKGROUND: Chronic subdural hematoma (CSDH) is a neurologic condition characterized as a hematoma in the subdural space with a period >3 weeks that primarily affects the elderly. Glucocorticoid, especially dexamethasone, either alone or combined with surgery, has been used to manage CSDH. We aimed to perform an updated systematic review and meta-analysis of the literature regarding the role of steroids in CSDH. METHODS: We searched the electronic databases PubMed, PubMed Central, Scopus, and Embase for relevant articles until December 2020. Study characteristics, quality, and end points were extracted, and analysis was performed by RevMan 5.4. RESULTS: The odds for subdural hematoma recurrence were decreased by 61% in the steroid group (odds ratio [OR], 0.39; confidence interval [CI], 0.19-0.79) compared with the control group. There was no significant difference in mortality during the study period (OR, 0.66; CI, 0.20-2.18), modified Rankin Scale score 0-3 (OR, 0.87; CI, 0.31-2.40), and modified Rankin Scale score 4-6 (OR, 1.15; CI, 0.42-3.18) between the 2 groups. However, pooling data from 3 studies showed 2.7 times higher odds of occurring adverse effects in steroid groups using the fixed-effect model (OR, 2.70; CI, 1.71-4.28). The treatment success was similar between the steroid and control groups (OR, 2.39; CI, 0.94-6.04). CONCLUSIONS: Treatment with steroids was associated with a lesser recurrence of CSDH. However, there was no benefit of steroid treatment in CSDH compared with nonsteroid treatment in terms of mortality and treatment success and some but significantly increased risk of adverse events.

Case report: 'Photodynamics of Subependymal Giant Cell Astrocytoma with 5-Aminolevulinic acid'.

Subependymal Giant Cell Astrocytoma (SEGA) is a common diagnosis in patients with Tuberous Sclerosis. Although surgical treatment is often required, resection may entail a significant risk for cognitive function given the anatomical relation with critical structures such as the fornices and subgenual area. Therefore, target subtotal resections using minimal invasive approaches focused in the higher metabolic areas are valuable options to preserve quality of life while addressing specific problems caused by the tumor, such as hydrocephalus or progressive growth of a specific component of the tumor. In this report, the authors explore the potential role of 5-ALA in the identification of highly metabolic areas during SEGA resection in the context of minimal invasive approaches.