Confocal laser endomicroscopy in glial tumors—a histomorphological analysis

Neurosurgical Review (2024) 47:65

The extent of resection and neurological outcome are important prognostic markers for overall survival in glioma patients. Confocal laser endomicroscopy is a tool to examine tissue without the need for fixation or staining. This study aims to analyze gliomas in confocal laser endomicroscopy and identify reliable diagnostic criteria for glial matter and glial tumors.

Material and methods One-hundred-and-five glioma specimens were analyzed using a 670-nm confocal laser endomicroscope and then processed into hematoxylin-eosin-stained frozen sections. All confocal images and frozen sections were evaluated for the following criteria: presence of tumor, cellularity, nuclear pleomorphism, changes of the extracellular glial matrix, microvascular proliferation, necrosis, and mitotic activity. Recurring characteristics were identified. Accuracy, sensitivity, specificity, and positive and negative predictive values were assessed for each feature.

Results All 125 specimens could be processed and successfully analyzed via confocal laser endomicroscopy. We found diagnostic criteria to identify white and grey matter and analyze cellularity, nuclear pleomorphism, changes in the glial matrix, vascularization, and necrosis in glial tumors. An accuracy of > 90.0 % was reached for grey matter, cellularity, and necrosis, > 80.0 % for white matter and nuclear pleomorphism, and > 70.0 % for microvascular proliferation and changes of the glial matrix. Mitotic activity could not be identified. Astroglial tumors showed significantly less nuclear pleomorphism in confocal laser endomicroscopy than oligodendroglial tumors (p < 0.001). Visualization of necrosis aids in the differentiation of low grade gliomas and high grade gliomas (p < 0.002).

Conclusion Autofluorescence-based confocal laser endomicroscopy proved not only useful in differentiation between tumor and brain tissue but also revealed useful clues to further characterize tissue without processing in a lab. Possible applications include the improvement of extent of resection and the safe harvest of representative tissue for histopathological and molecular genetic diagnostics.

Confocal laser endomicroscopy in glial tumors—a histomorphological analysis

Neurosurgical Review (2024) 47:65

The extent of resection and neurological outcome are important prognostic markers for overall survival in glioma patients. Confocal laser endomicroscopy is a tool to examine tissue without the need for fixation or staining. This study aims to analyze gliomas in confocal laser endomicroscopy and identify reliable diagnostic criteria for glial matter and glial tumors.

Material and methods One-hundred-and-five glioma specimens were analyzed using a 670-nm confocal laser endomicroscope and then processed into hematoxylin-eosin-stained frozen sections. All confocal images and frozen sections were evaluated for the following criteria: presence of tumor, cellularity, nuclear pleomorphism, changes of the extracellular glial matrix, microvascular proliferation, necrosis, and mitotic activity. Recurring characteristics were identified. Accuracy, sensitivity, specificity, and positive and negative predictive values were assessed for each feature.

Results All 125 specimens could be processed and successfully analyzed via confocal laser endomicroscopy. We found diagnostic criteria to identify white and grey matter and analyze cellularity, nuclear pleomorphism, changes in the glial matrix, vascularization, and necrosis in glial tumors. An accuracy of > 90.0 % was reached for grey matter, cellularity, and necrosis, > 80.0 % for white matter and nuclear pleomorphism, and > 70.0 % for microvascular proliferation and changes of the glial matrix. Mitotic activity could not be identified. Astroglial tumors showed significantly less nuclear pleomorphism in confocal laser endomicroscopy than oligodendroglial tumors (p < 0.001). Visualization of necrosis aids in the differentiation of low grade gliomas and high grade gliomas (p < 0.002).

Conclusion Autofluorescence-based confocal laser endomicroscopy proved not only useful in differentiation between tumor and brain tissue but also revealed useful clues to further characterize tissue without processing in a lab. Possible applications include the improvement of extent of resection and the safe harvest of representative tissue for histopathological and molecular genetic diagnostics.

Proposal of a new grading system for meningioma resection: the Copenhagen Protocol

Acta Neurochirurgica (2022) 164:229–238

The extent of meningioma resection is the most fundamental risk factor for recurrence, and exact knowledge of extent of resection is necessary for prognostication and for planning of adjuvant treatment. Currently used classifications are the EANO-grading and the Simpson grading. The former comprises radiological imaging with contrast-enhanced MRI and differentiation between “gross total removal” and “subtotal removal,” while the latter comprises a five-tiered differentiation of the surgeon’s impression of the extent of resection. The extent of resection of tumors is usually defined via analyses of resection margins but has until now not been implemented for meningiomas. PET/MRI imaging with 68Ga-DOTATOC allows more sensitive and specific imaging than MRI following surgery of meningiomas.

Objective To develop an objective grading system based on microscopic analyses of resection margins and sensitive radiological analyses to improve management of follow-up, adjuvant therapy, and prognostication of meningiomas. Based on the rationale of resection-margin analyses as gold standard and superior imaging performance of 68Ga DOTATOC PET, we propose “Copenhagen Grading” for meningiomas.

Results Copenhagen Grading was described for six pilot patients with examples of positive and negative findings on histopathology and DOTATOC PET scanning. The grading could be traceably implemented and parameters of grading appeared complementary. Copenhagen Grading is prospectively implemented as a clinical standard at Rigshospitalet, Copenhagen.

Conclusion Copenhagen Grading provided a comprehensive, logical, and reproducible definition of the extent of resection. It offers promise to be the most sensitive and specific imaging modality available for meningiomas. Clinical and cost-efficacy remain to be established during prospective implementation.

Intraoperative 3D ultrasound–guided resection of diffuse low-grade gliomas

J Neurosurg 132:518–529, 2020

Extent of resection (EOR) and residual tumor volume are linked to prognosis in low-grade glioma (LGG) and there are various methods for facilitating safe maximal resection in such patients. In this prospective study the authors assess radiological and clinical results in consecutive patients with LGG treated with 3D ultrasound (US)–guided resection under general anesthesia.

METHODS Consecutive LGGs undergoing primary surgery guided with 3D US between 2008 and 2015 were included. All LGGs were classified according to the WHO 2016 classification system. Pre- and postoperative volumetric assessments were performed, and volumetric results were linked to overall and malignant-free survival. Pre- and postoperative health-related quality of life (HRQoL) was evaluated.

RESULTS Forty-seven consecutive patients were included. Twenty LGGs (43%) were isocitrate dehydrogenase (IDH)– mutated, 7 (14%) were IDH wild-type, 19 (40%) had both IDH mutation and 1p/19q codeletion, and 1 had IDH mutation and inconclusive 1p/19q status. Median resection grade was 93.4%, with gross-total resection achieved in 14 patients (30%). An additional 24 patients (51%) had small tumor remnants < 10 ml. A more conspicuous tumor border (p = 0.02) and lower University of California San Francisco prognostic score (p = 0.01) were associated with less remnant tumor tissue, and overall survival was significantly better with remnants < 10 ml (p = 0.03). HRQoL was maintained or improved in 86% of patients at 1 month. In both cases with severe permanent deficits, relevant ischemia was present on diffusionweighted postoperative MRI.

CONCLUSIONS Three-dimensional US–guided LGG resections under general anesthesia are safe and HRQoL is preserved in most patients. Effectiveness in terms of EOR appears to be consistent with published studies using other advanced neurosurgical tools. Avoiding intraoperative vascular injury is a key factor for achieving good functional outcome.

Parietal association deficits in patients harboring parietal lobe gliomas

J Neurosurg 130:773–779, 2019

Although the parietal lobe is a common site for glioma formation, current literature is scarce, consists of retrospective studies, and lacks consistency with regard to the incidence, nature, and severity of parietal association deficits (PADs).

The aim of this study was to assess the characteristics and incidence of PADs in patients suffering from parietal lobe gliomas through a prospective study and a battery of comprehensive neuropsychological tests.

METHODS Between 2012 and 2016 the authors recruited 38 patients with glioma confined in the parietal lobe. Patients were examined for primary and secondary association deficits with a dedicated battery of neuropsychological tests. The PADs were grouped into 5 categories: visuospatial attention, gnosis, praxis, upper-limb coordination, and language. For descriptive analysis tumors were divided into high- and low-grade gliomas and also according to patient age and tumor size.

RESULTS Parietal association deficits were elicited in 80% of patients, thus being more common than primary deficits (50%). Apraxia was the most common PAD (47.4%), followed by anomic aphasia and subcomponents of Gerstmann’s syndrome (34.2% each). Other deficits such as hemineglect, stereoagnosia, extinction, and visuomotor ataxia were also detected, albeit at lower rates. There was a statistically nonsignificant difference between PADs and sex (72.2% males, 85% females) and age (77.8% at ≤ 60 years, 80% at age > 60 years), but a statistically significant difference between the > 4 cm and the ≤ 4 cm diameter group (p = 0.02, 94.7% vs 63.2%, respectively). There was a tendency (p = 0.094) for low-grade gliomas to present with fewer PADs (50%) than high-grade gliomas (85.7%). Tumor laterality showed a strong correlation with hemineglect (p = 0.004, predilection for right hemisphere), anomia (p = 0.001), and Gerstmann’s symptoms (p = 0.01); the last 2 deficits showed a left (dominant) hemispheric preponderance.

CONCLUSIONS This is the first study to prospectively evaluate the incidence and nature of PADs in patients with parietal gliomas. It could be that the current literature may have underestimated the true incidence of deficits. Dedicated neuropsychological examination detects a high frequency of PADs, the most common being apraxia, followed by anomia and subcomponents of Gerstmann’s syndrome. Nevertheless, a direct correlation between the clinical deficit and its anatomical substrate is only possible to a limited extent, highlighting the need for intraoperative cortical and subcortical functional mapping.

Stereotactic laser ablation as treatment for brain metastases that recur after stereotactic radiosurgery

stereotactic-laser-ablation-for-brain-metastases

Neurosurg Focus 41 (4):E11, 2016

Therapeutic options for brain metastases (BMs) that recur after stereotactic radiosurgery (SRS) remain limited. Methods The authors provide the collective experience of 4 institutions where treatment of BMs that recurred after SRS was performed with stereotactic laser ablation (SLA).

Results Twenty-six BMs (in 23 patients) that recurred after SRS were treated with SLA (2 patients each underwent 2 SLAs for separate lesions, and a third underwent 2 serial SLAs for discrete BMs). Histological findings in the BMs treated included the following: breast (n = 6); lung (n = 6); melanoma (n = 5); colon (n = 2); ovarian (n = 1); bladder (n = 1); esophageal (n = 1); and sarcoma (n = 1). With a median follow-up duration of 141 days (range 64–794 days), 9 of the SLA-treated BMs progressed despite treatment (35%). All cases of progression occurred in BMs in which < 80% ablation was achieved, whereas no disease progression was observed in BMs in which ≥ 80% ablation was achieved. Five BMs were treated with SLA, followed 1 month later by adjuvant SRS (5 Gy daily × 5 days). No disease progression was observed in these patients despite ablation efficiency of < 80%, suggesting that adjuvant hypofractionated SRS enhances the efficacy of SLA. Of the 23 SLA-treated patients, 3 suffered transient hemiparesis (13%), 1 developed hydrocephalus requiring temporary ventricular drainage (4%), and 1 patient who underwent SLA of a 28.9-cm3 lesion suffered a neurological deficit requiring an emergency hemicraniectomy (4%). Although there is significant heterogeneity in corticosteroid treatment post-SLA, most patients underwent a 2-week taper.

Conclusions Stereotactic laser ablation is an effective treatment option for BMs in which SRS fails. Ablation of ≥ 80% of BMs is associated with decreased risk of disease progression. The efficacy of SLA in this setting may be augmented by adjuvant hypofractionated SRS.

Graph theory, complex networks, and neurosurgery

Graph theory analysis of complex brain networks

J Neurosurg 124:1665–1678, 2016

Neuroanatomy has entered a new era, culminating in the search for the connectome, otherwise known as the brain’s wiring diagram. While this approach has led to landmark discoveries in neuroscience, potential neurosurgical applications and collaborations have been lagging.

In this article, the authors describe the ideas and concepts behind the connectome and its analysis with graph theory. Following this they then describe how to form a connectome using resting state functional MRI data as an example. Next they highlight selected insights into healthy brain function that have been derived from connectome analysis and illustrate how studies into normal development, cognitive function, and the effects of synthetic lesioning can be relevant to neurosurgery.

Finally, they provide a précis of early applications of the connectome and related techniques to traumatic brain injury, functional neurosurgery, and neurooncology.