Intraoperative confocal laser endomicroscopy: prospective in vivo feasibility study of a clinical-grade system for brain tumors

J Neurosurg 138:587–597, 2023

The authors evaluated the feasibility of using the first clinical-grade confocal laser endomicroscopy (CLE) system using fluorescein sodium for intraoperative in vivo imaging of brain tumors.

METHODS A CLE system cleared by the FDA was used in 30 prospectively enrolled patients with 31 brain tumors (13 gliomas, 5 meningiomas, 6 other primary tumors, 3 metastases, and 4 reactive brain tissue). A neuropathologist classified CLE images as interpretable or noninterpretable. Images were compared with corresponding frozen and permanent histology sections, with image correlation to biopsy location using neuronavigation. The specificities and sensitivities of CLE images and frozen sections were calculated using permanent histological sections as the standard for comparison. A recently developed surgical telepathology software platform was used in 11 cases to provide real-time intraoperative consultation with a neuropathologist.

RESULTS Overall, 10,713 CLE images from 335 regions of interest were acquired. The mean duration of the use of the CLE system was 7 minutes (range 3–18 minutes). Interpretable CLE images were obtained in all cases. The first interpretable image was acquired within a mean of 6 (SD 10) images and within the first 5 (SD 13) seconds of imaging; 4896 images (46%) were interpretable. Interpretable image acquisition was positively correlated with study progression, number of cases per surgeon, cumulative length of CLE time, and CLE time per case (p ≤ 0.01). The diagnostic accuracy, sensitivity, and specificity of CLE compared with frozen sections were 94%, 94%, and 100%, respectively, and the diagnostic accuracy, sensitivity, and specificity of CLE compared with permanent histological sections were 92%, 90%, and 94%, respectively. No difference was observed between lesion types for the time to first interpretable image (p = 0.35). Deeply located lesions were associated with a higher percentage of interpretable images than superficial lesions (p = 0.02). The study met the primary end points, confirming the safety and feasibility and acquisition of noninvasive digital biopsies in all cases. The study met the secondary end points for the duration of CLE use necessary to obtain interpretable images. A neuropathologist could interpret the CLE images in 29 (97%) of 30 cases.

CONCLUSIONS The clinical-grade CLE system allows in vivo, intraoperative, high-resolution cellular visualization of tissue microstructure and identification of lesional tissue patterns in real time, without the need for tissue preparation.

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.

Diastematomyelia: A 35-Year Experience


SPINE Volume 38, Number 6, pp E344–E349

Diastematomyelia is a rare entity, which presents distinct clinical characteristics and requires different managements compared with other more common occult spinal dysraphism.

Methods. A total of 156 patients with diastematomyelia were reviewed. All the patients underwent neurological and radiological examinations. Surgical excision of the lesion was performed for most patients and intradural exploration of the lumbar region was done to release tethering of conus in some patients. One patient died and autopsy was performed. Follow-up was carried out for all the patients, including surgical and nonsurgical approaches.

Results. There were 123 cases of type I diastematomyelia and 33 cases of type II diastematomyelia. The lumbar and thoracolumbar region was the most common site for diastematomyelia, and most spinal cords were split among 6 segments. The postoperative course was complicated by cerebrospinal fl uid leakage in 2 patients, temporary neurological deterioration in 4 patients, and epidural hematoma in 1 patient. All cases did not have aggravation of symptoms during the follow-up of 2 to 20 years (mean of 4.5 yr). For the 123 patients with type I diastematomyelia, clinical symptoms were improved in 96 after surgical intervention and no worsening or occurrence of new clinical signs were observed during the follow-up. Those who did not receive surgery showed stabilization of neurological manifestation. Of the 33 type II cases, 9 surgical patients remained neurologically stable during the postoperative years without signifi cant improvement in function, and 24 nonsurgical patients neither improved nor worsened in their neural defi cit.

Conclusion. Surgical treatment is the necessary management for type I diastematomyelia causing progressive neurological deterioration or with tethered fi lum, whereas conservative treatment is recommended to asymptomatic type I diastematomyelia and all type II diastematomyelia.

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