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Circulating Tumor DNA in Adults With Glioma: A Systematic Review and Meta-Analysis of Biomarker Performance

Neurosurgery 91:231–238, 2022

Circulating tumor DNA (ctDNA) has emerged as a promising noninvasive biomarker to capture tumor genetics in patients with brain tumors. Research into its clinical utility, however, has not been standardized because the sensitivity and specificity of ctDNA remain undefined.

OBJECTIVE: To (1) review the primary literature about ctDNA in adults with glioma to compare the sensitivity and specificity of ctDNA in the cerebrospinal fluid vs the plasma and (2) to evaluate the effect of tumor grade on detection of ctDNA.

METHODS: PRISMA-guided systematic review and meta-analysis was performed using published studies that assessed ctDNA in either plasma or cerebrospinal fluid among adult patients with confirmed glioma. Summary receiver operating characteristic curves were generated using the Rücker-Schumacher method, and area under the curve (AUC) was calculated.

RESULTS: Meta-analysis revealed improved biomarker performance for CSF (AUC = 0.947) vs plasma (AUC = 0.741) ctDNA, although this did not reach statistical significance (P = .141). Qualitative analysis revealed greater sensitivities among single-allele PCR and small, targeted next-generation sequencing panels compared with broader panels. It additionally demonstrated higher sensitivity of ctDNA detection in high-grade vs low-grade gliomas, although these analyses were limited by a lack of specificity reporting in many studies.

CONCLUSION: ctDNA seems to be a highly sensitive and specific noninvasive biomarker among adults with gliomas. To maximize its performance, CSF should be studied with targeted genetic analysis platforms, particularly in high-grade gliomas. Further studies on ctDNA are needed to define its clinical utility in diagnosis, prognostication, glioblastoma pseudoprogression, and other scenarios wherein neoadjuvant therapies may be considered.

KEY WORDS: Cell-free DNA, Circulating tumor DNA, CNS tumor, Glioma, Liquid biopsy

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Risk factors of recurrence in chronic subdural hematoma and a proposed extended classification of internal architecture as a predictor of recurrence

Neurosurgical Review (2022) 45:2777–2786

Chronic subdural hematomas (cSDHs) constitute one of the most prevalent intracranial disease entities requiring surgical treatment. Although mostly taking a benign course, recurrence after treatment is common and associated with additional morbidity and costs.

Aim of this study was to develop hematoma-specific characteristics associated with risk of recurrence. All consecutive patients treated for cSDH in a single university hospital between 2015 and 2019 were retrospectively considered for inclusion. Size, volume, and midline shift were noted alongside relevant patient-specific factors. We applied an extended morphological classification system based on internal architecture in CT imaging consisting of eight hematoma subtypes. A logistic regression model was used to assess the classification’s performance on predicting hematoma recurrence.

Recurrence was observed in 122 (32.0%) of 381 included patients. Apart from postoperative depressed brain volume (OR 1.005; 95% CI 1.000 to 1.010; p = 0.048), neither demographic nor factors related to patient comorbidity affected recurrence. The extended hematoma classification was identified as a significant predictor of recurrence (OR 1.518; 95% CI 1.275 to 1.808; p < 0.001). The highest recurrence rates were observed in hematomas of the homogenous (isodense: 41.4%; hypodense: 45.0%) and sedimented (50.0%) types.

Our results support that internal architecture subtypes might represent stages in the natural history of chronic subdural hematoma. Detection and treatment at a later stage of spontaneous repair can result in a reduced risk of recurrence. Based on their high risk of recurrence, we advocate follow-up after treatment of sedimented and homogenous hematomas.

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Can artificial intelligence support or even replace physicians in measuring sagittal balance?

European Spine Journal (2022) 31:1943–1951

Sagittal balance (SB) plays an important role in the surgical treatment of spinal disorders. The aim of this research study is to provide a detailed evaluation of a new, fully automated algorithm based on artificial intelligence (AI) for the determination of SB parameters on a large number of patients with and without instrumentation.

Methods Pre- and postoperative sagittal full body radiographs of 170 patients were measured by two human raters, twice by one rater and by the AI algorithm which determined: pelvic incidence, pelvic tilt, sacral slope, L1-S1 lordosis, T4-T12 thoracic kyphosis (TK) and the spino-sacral angle (SSA). To evaluate the agreement between human raters and AI, the mean error (95% confidence interval (CI)), standard deviation and an intra- and inter-rater reliability was conducted using intra-class correlation (ICC) coefficients.

Results ICC values for the assessment of the intra- (range: 0.88–0.97) and inter-rater (0.86–0.97) reliability of human raters are excellent. The algorithm is able to determine all parameters in 95% of all pre- and in 91% of all postoperative images with excellent ICC values (PreOP-range: 0.83–0.91, PostOP: 0.72–0.89). Mean errors are smallest for the SSA (PreOP: −0.1° (95%-CI: −0.9°–0.6°); PostOP: −0.5° (−1.4°–0.4°)) and largest for TK (7.0° (6.1°–7.8°); 7.1° (6.1°–8.1°)).

Conclusion A new, fully automated algorithm that determines SB parameters has excellent reliability and agreement with human raters, particularly on preoperative full spine images. The presented solution will relieve physicians from timeconsuming routine work of measuring SB parameters and allow the analysis of large databases efficiently.

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Prognostic data analysis of surgical treatments for intracerebral hemorrhage

Neurosurgical Review (2022) 45:2733–2744

Spontaneous intracerebral hemorrhage (ICH) is a commonly occurring disease in neurosurgery, yet its surgical treatment is controversial.

This paper pertains to the study of the effects of different treatment regimens on the outcome of ICH population. Based on a globally shared third-party MIMIC-III database, the researchers firstly described the dissimilarities in survival probability, mortality, and neurological recovery among mainstream treatments for ICH; secondly, patient classification was determined by important clinical features; and outcome variations among treatment groups were compared.

The 28-day, 90-day, and in-hospital mortality in the craniotomy group were significantly lower than minimally invasive surgery (MIS) and non-surgical group patients; and, the medium/long-term mortality in MIS group was significantly lower than the non-surgical group. The craniotomy group positively correlated with short-term GCS recovery compared with the MIS group; no difference existed between the non-surgical and MIS groups. The craniotomy group 90-day survival probability and short-term GCS recovery were superior to the other two treatments in the subgroups of first GCS 3–12; this tendency also presented in the MIS group over non-surgical group. For milder patients (first GCS > 12), the three treatment regimens had a minimal effect on patient survival, but the non-surgical group showed an advantage in short-term GCS recovery.

Craniotomy patients have a lower mortality and a better short-term neurological recovery in an ICH population, especially in short-to-medium term mortality and short-term neurological recovery over MIS patients. In addition, surgical treatment is recommendable for patients with a GCS ≤ 12.

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Characteristics of Sagittal Spinopelvic Alignment Changes After Symptom Relief After Simple Lumbar Decompression

 Neurosurgery 91:331–338, 2022

Sagittal spinopelvic alignment (SSPA) parameters are essential for the diagnosis of adult spinal deformities (ASDs) and their progression. Certain clinical symptoms that occur in patients with lumbar spinal stenosis (LSS) and herniated nucleus pulposus (HNP) may distort the SSPA and mimic ASD.

OBJECTIVE: To differentiate SSPA in symptomatic patients from asymptomatic patients within 10 minutes in the standing position.

METHODS: This retrospective cohort study evaluated changes in SSPA after simple lumbar decompression surgery in patients with LSS and HNP. Relative sagittal alignment (RSA), relative pelvic version, relative lumbar lordosis (RLL), Lordosis Distribution Index (LDI), and global alignment and proportion (GAP) values were calculated using the conventional Schwab classification method. First, the preoperative and postoperative SSPA parameters were compared. Second, patients were subgrouped into symptomatic within 10 minutes of standing (SP group) and other symptoms of LSS and HNP as controls. Changes in SSPA parameters after symptom relief after simple lumbar decompression surgery were compared between the two groups.

RESULTS: Overall, all SSPA parameters improved after surgery. However, after subgrouping, patients in the control group did not show significant SSPA alterations, except for LDI, whereas patients in the SP group significantly improved in terms of their RSA, RLL, LDI, and GAP values after symptom relief after surgery.

CONCLUSION: Patients with pain on standing within 10 minutes showed significant correction in RSA, RLL, and GAP values after simple lumbar decompression. Therefore, it is important to observe such clinical symptoms to avoid misdiagnosis of ASD.

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Data fusion and 3D visualization for optimized representation of neurovascular relationships in the posterior fossa

Acta Neurochirurgica (2022) 164:2141–2151

Reliable 3D visualization of neurovascular relationships in the posterior fossa at the surface of the brainstem is still critical due to artifacts of imaging. To assess neurovascular compression syndromes more reliably, a new approach of 3D visualization based on registration and fusion of high-resolution MR data is presented.

Methods A total of 80 patients received MRI data with 3D-CISS and 3D-TOF at 3.0 Tesla. After registration and subsequent segmentation, the vascular information of the TOF data was fused into the CISS data. Two 3D visualizations were created for each patient, one before and one after fusion, which were verified with the intraoperative situation during microvascular decompression (MVD). The reproduction quality of vessels was evaluated with a rating system.

Results In all cases, the presented approach compensated for typical limitations in the 3D visualization of neurovascular compression such as the partial or complete suppression of larger vessels, suppression of smaller vessels at the CSF margin, and artifacts from heart pulsation. In more than 95% of the cases of hemifacial spasm and glossopharyngeal neuralgia, accurate assessment of the compression was only possible after registration and fusion. In more than 50% of the cases with trigeminal neuralgia, the presented approach was crucial to finding the actually offending vessel.

Conclusions 3D visualization of fused image data allows for a more complete representation of the vessel-nerve situation. The results from this approach are reproducible and the assessment of neurovascular compression is safer. It is a powerful tool for planning MVD.

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Stereotactic Radiofrequency Thermocoagulation of Hypothalamic Hamartomas With Bilateral Attachments to the Hypothalamus

Neurosurgery 91:295–303, 2022

Disconnection surgery for the treatment of epileptic hypothalamic hamartomas (HHs) is strategically difficult in cases with complex-shaped HHs, especially with bilateral hypothalamic attachments, despite its effectiveness.

OBJECTIVE: To evaluate the feasibility of a new approach for stereotactic radiofrequency thermocoagulation (SRT) using penetration of the third ventricle (SRT-TT) aiming to disconnect bilateral hypothalamic attachments in a single-staged, unilateral procedure.

METHODS: Ninety patients (median age at surgery, 5.0 years) who had HHs with bilateral hypothalamic attachments and were followed for at least 1 year after their last SRT were retrospectively reviewed.

RESULTS: Thirty-three patients underwent SRT-TT as initial surgery. Of the 58 patients after mid-2013 when SRT-TT was introduced, 33 underwent SRT-TT and 12 (20.7%) required reoperation (ReSRT), whereas 20 of 57 patients (35.1%) without SRT-TT underwent reoperation. Reoperation was required in significantly fewer patients aftermid-2013 (n = 12 of 58, 20.7%) than before mid-2013 (n = 15 of 32, 46.9%) (P = .01). Final seizure freedoms were not different between before and aftermid-2013 (gelastic seizure freedom, n = 30 [93.8%] vs n = 49 [84.5%] and other types of seizure freedom, n = 21 of 31 [67.7%] vs n = 32 of 38 [84.2%]). Persistent complications were less in SRT-TT than in ReSRT using the bilateral approach, but not significantly. However, hormonal replacement was required significantly more often in ReSRT using the bilateral approach (4 of 9, 44.4%) than in SRT-TT (3 of 32, 9.4%) (P = .01).

CONCLUSION: SRT-TT enabled disconnection of bilateral attachments of HHs in a singlestaged procedure, which reduced the additional invasiveness of reoperation. Moreover, SRT-TT reduced damage to the contralateral hypothalamus, with fewer endocrinological complications than the bilateral approach.

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Role of the parietooccipital fissure and its implications in the pathophysiology of posterior medial temporal gliomas

J Neurosurg 137:505–514, 2022

The parietooccipital fissure is an anatomical landmark that divides the temporal, occipital, and parietal lobes. More than 40% of gliomas are located in these three lobes, and the temporal lobe is the most common location. The parietooccipital fissure is located just posterior to the medial temporal lobe, but little is known about the clinical significance of this fissure in gliomas. The authors investigated the anatomical correlations between the parietooccipital fissure and posterior medial temporal gliomas to reveal the radiological features and unique invasion patterns of these gliomas.

METHODS The authors retrospectively reviewed records of all posterior medial temporal glioma patients treated at their institutions and examined the parietooccipital fissure. To clarify how the surrounding structures were invaded in each case, the authors categorized tumor invasion as being toward the parietal lobe, occipital lobe, isthmus of the cingulate gyrus, insula/basal ganglia, or splenium of the corpus callosum. DSI Studio was used to visualize the fiber tractography running through the posterior medial temporal lobe.

RESULTS Twenty-four patients with posterior medial temporal gliomas were identified. All patients presented with a parietooccipital fissure as an uninterrupted straight sulcus and as the posterior border of the tumor. Invasion direction was toward the parietal lobe in 13 patients, the occipital lobe in 4 patients, the isthmus of the cingulate gyrus in 19 patients, the insula/basal ganglia in 3 patients, and the splenium of the corpus callosum in 8 patients. Although the isthmus of the cingulate gyrus and the occipital lobe are located just posterior to the posterior medial temporal lobe, there was a significantly greater preponderance of invasion toward the isthmus of the cingulate gyrus than toward the occipital lobe (p = 0.00030, McNemar test). Based on Schramm’s classification for the medial temporal tumors, 4 patients had type A and 20 patients had type D tumors. The parietooccipital fissure determined the posterior border of the tumors, resulting in a unique and identical radiological feature. Diffusion spectrum imaging (DSI) tractography indicated that the fibers running through the posterior medial temporal lobe toward the occipital lobe had to detour laterally around the bottom of the parietooccipital fissure.

CONCLUSIONS Posterior medial temporal gliomas present identical invasion patterns, resulting in unique radiological features that are strongly affected by the parietooccipital fissure. The parietooccipital fissure is a key anatomical landmark for understanding the complex infiltrating architecture of posterior medial temporal gliomas.

 

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A new simple and free tubular device for microscopic transcortical approach to deep‑seated lesions

Acta Neurochirurgica (2022) 164:2049–2055

Surgery for deep-seated brain tumors remains challenging. Transcortical approaches often require brain retraction to ensure an adequate surgical corridor, thus possibly leading to brain damage. Various techniques have been developed to minimize brain retraction such as self-retaining retractors, endoscopic approaches, or tubular retractor systems. Even if they evenly distribute the mechanical pressure over the parenchyma, rigid retractors can also cause some degree of brain damage and have significant disadvantages. We propose here a soft cottonoid retractor for microscopic resection of deepseated and ventricular lesions.

Methods Through a small corticectomy, a channel route with a blunt cannula is developed until the lesion is reached. Then, a “balloon-like system” made with a surgical glove is progressively inflated, dilatating the surgical corridor. A mini-tubular device, handmade by suturing a surgical cottonoid, is positioned into the corridor, unfolded, and sutured to the edge of the dura, to prevent it from being progressively expelled from the working channel. This allows a good visualization of the lesion and surrounding structures under the microscope.

Results Advantages of this technique are the softness of the tube walls, the absence of rigid arm to hold the tube, and the possibility for the tube to follow the movements of the instruments and to modify its orientation according to the working area.

Conclusion This simple and inexpensive tubular working channel for microscopic transcortical approach is a valuable alternative technique to traditional self-retaining retractor and rigid tube for the microsurgical resection of deep-seated brain tumors.

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Acute Postoperative Seizures and Engel Class Outcome at 1 Year Postselective Laser Amygdalohippocampal Ablation for Mesial Temporal Lobe Epilepsy

Neurosurgery 91:347–354, 2022

MRI-guided laser interstitial thermal therapy (MRgLITT) for mesial temporal lobe epilepsy is a safe, minimally invasive alternative to traditional surgical approaches. Prognostic factors associated with efficacy are debated; preoperative epilepsy duration and semiology seem to be important variables.

OBJECTIVE: To determine whether acute postoperative seizure (APOS) after MRgLITT for mesial temporal lobe epilepsy is associated with seizure freedom/Engel class outcome at 1 year.

METHODS: A single-institution retrospective study including adults undergoing first time MRgLITT for mesial temporal lobe epilepsy (2010-2019) with ≥1-year follow-up. Preoperative data included sex, epilepsy duration, number of antiepileptics attempted, weekly seizure frequency, seizure semiology, and radiographically verified anatomic lesion at seizure focus. Postoperative data included clinical detection of APOS within 7 days postoperatively, and immediate amygdala, hippocampal, entorhinal, and parahippocampal residual volumes determined using quantitative imaging postprocessing. Primary outcome was seizure freedom/Engel classification 1 year postoperatively.

RESULTS: Of 116 patients, 53%(n = 61) were female, with an average epilepsy duration of 21 (±14) years, average 6 failed antiepileptics (±3), and weekly seizure frequency of 5. APOS was associated with worse Engel class (P = .010), conferring 6.3 times greater odds of having no improvement vs achieving seizure freedom at 1 year. Residual amygdala, hippocampal, entorhinal, and parahippocampal volumes were not statistically significant prognostic factors.

CONCLUSION: APOS was associated with a lower chance of seizure freedom at 1 year post-MRgLITT for mesial temporal lobe epilepsy. Amygdala, hippocampal, entorhinal, and parahippocampal residual volumes after ablation were not significant prognostic factors.

 

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3D printing applications in spine surgery: an evidence‑based assessment toward personalized patient care

European Spine Journal (2022) 31:1682–1690

Spine surgery entails a wide spectrum of complicated pathologies. Over the years, numerous assistive tools have been introduced to the modern neurosurgeon’s armamentarium including neuronavigation and visualization technologies. In this review, we aimed to summarize the available data on 3D printing applications in spine surgery as well as an assessment of the future implications of 3D printing.

Methods We performed a comprehensive review of the literature on 3D printing applications in spine surgery.

Results Over the past decade, 3D printing and additive manufacturing applications, which allow for increased precision and customizability, have gained significant traction, particularly spine surgery. 3D printing applications in spine surgery were initially limited to preoperative visualization, as 3D printing had been primarily used to produce preoperative models of patient-specific deformities or spinal tumors. More recently, 3D printing has been used intraoperatively in the form of 3D customizable implants and personalized screw guides.

Conclusions Despite promising preliminary results, the applications of 3D printing are so recent that the available data regarding these new technologies in spine surgery remains scarce, especially data related to long-term outcomes.

 

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Change in sagittal alignment after decompression alone in patients with lumbar spinal stenosis without significant deformity

J Neurosurg Spine 37:57–63, 2022

The authors’ objective was to investigate whether sagittal balance improves in patients with spinal stenosis after decompression alone.

METHODS This prospective longitudinal cohort study compared preoperative and 6-month postoperative 36-inch full-length radiographs in patients aged older than 60 years. Patients underwent decompression alone for central lumbar spinal stenosis with either a minimally invasive bilateral laminotomy for central decompression, unilateral laminectomy as an over-the-top procedure for bilateral decompression, or traditional wide laminectomy with removal of the spinous processes on both sides. The following radiographic parameters were measured: sagittal vertical axis (SVA), lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), PI-LL mismatch, coronal Cobb angle, and sacral slope (SS). Patient reported outcome measures (PROMs) were collected, including scores on the Oswestry Disability Index (ODI), visual analog scale (VAS) for leg and back pain, and EQ-5D.

RESULTS Forty-five patients (24 males) with a mean ± SD age of 71.8 ± 5.6 years were included. Sagittal balance showed statistically significant improvement, with the mean SVA decreasing from 52.3 mm preoperatively to 33.9 mm postoperatively (p = 0.0001). The authors found an increase in LL, from mean −41.5° preoperatively to −43.9° postoperatively, but this was not statistically significant (p = 0.055). A statistically significant decrease in PI-LL mismatch from mean 8.4° preoperatively to 5.8° postoperatively was found (p = 0.002). All PROM scores showed significant improvement after spinal decompression surgery. The correlations between SVA and all PROMs were statistically significant at both preoperative and postoperative time points, although most correlations were weak except for those between preoperative SVA and ODI (r = 0.55) and between SVA and VAS for leg pain (r = 0.58).

CONCLUSIONS Sagittal balance and PROMs show improvement at short-term follow-up evaluations in patients who have undergone decompression alone for lumbar spinal stenosis.

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Change in sagittal alignment after decompression alone in patients with lumbar spinal stenosis without significant deformity: a prospective cohort study

J Neurosurg Spine 37:57–63, 2022

OBJECTIVE The authors’ objective was to investigate whether sagittal balance improves in patients with spinal stenosis after decompression alone.

METHODS This prospective longitudinal cohort study compared preoperative and 6-month postoperative 36-inch full-length radiographs in patients aged older than 60 years. Patients underwent decompression alone for central lumbar spinal stenosis with either a minimally invasive bilateral laminotomy for central decompression, unilateral laminectomy as an over-the-top procedure for bilateral decompression, or traditional wide laminectomy with removal of the spinous processes on both sides. The following radiographic parameters were measured: sagittal vertical axis (SVA), lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), PI-LL mismatch, coronal Cobb angle, and sacral slope (SS). Patient reported outcome measures (PROMs) were collected, including scores on the Oswestry Disability Index (ODI), visual analog scale (VAS) for leg and back pain, and EQ-5D.

RESULTS Forty-five patients (24 males) with a mean ± SD age of 71.8 ± 5.6 years were included. Sagittal balance showed statistically significant improvement, with the mean SVA decreasing from 52.3 mm preoperatively to 33.9 mm postoperatively (p = 0.0001). The authors found an increase in LL, from mean −41.5° preoperatively to −43.9° postoperatively, but this was not statistically significant (p = 0.055). A statistically significant decrease in PI-LL mismatch from mean 8.4° preoperatively to 5.8° postoperatively was found (p = 0.002). All PROM scores showed significant improvement after spinal decompression surgery. The correlations between SVA and all PROMs were statistically significant at both preoperative and postoperative time points, although most correlations were weak except for those between preoperative SVA and ODI (r = 0.55) and between SVA and VAS for leg pain (r = 0.58).

CONCLUSIONS Sagittal balance and PROMs show improvement at short-term follow-up evaluations in patients who have undergone decompression alone for lumbar spinal stenosis.

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A systematic review with meta‑analysis of the diagnostic test accuracy of pedicle screw electrical stimulation

European Spine Journal (2022) 31:1599–1610

Purpose To provide a systematic review with meta-analysis providing evidence of the current diagnostic test accuracy (DTA) of pedicle screw electrical stimulation.

Methods A systematic database search on PubMed, Scopus and Web of Science was performed according to the PRISMADTA guidelines, and eligibility criteria applied to reduce the results to: (1) only journal articles reporting electrical stimulation of the pedicle screw head, (2) screw position confirmation by imaging techniques, and (3) enough information allowing the calculation of a 2 × 2 contingency table. Sample characteristics, image confirmation method, electrical current threshold and stimulation results were retrieved and analyzed using according to appropriate DTA analysis methods, and allowing the calculation of specificity, sensitivity for pedicle screws insertion at the lumbar and thoracic levels.

Results Lumbar screw stimulation presents a higher sensitivity (0.586 [0.336, 0.798] and specificity (0.984 [0.958, 0.994]) than thoracic screws (sensitivity: 0.270 [0.096; 0.562]; specificity: 0.958 [0.931, 0.975]). The same is observed in terms of the diagnostic odds ratio for lumbar (88.32 [32.136, 242.962]) and thoracic (8.460 [2.139, 33.469]) levels. When performing a sub-group analysis, it is possible to divide the lumbar stimulation threshold as 8 and 10–12 mA, and the thoracic threshold as 6 and 9–12 mA. A threshold of 8 mA at the lumbar level provides higher sensitivity and specificity. Increasing the threshold results in higher specificity but not sensitivity. In fact, at the range of 10–12 mA, the diagnostic validity is too low to confer this technique any robust diagnostic validity. Similarly, at the thoracic level, lower threshold currents are associated with increased sensitivity, but their diagnostic validity is very low.

Conclusion Electrical stimulation of the pedicle screw can be used as an adequate diagnostic capability at the lumbar level with a threshold of 8 mA. However, thoracic stimulation is currently not reliable, with very low sensitivity and diagnostic validity at 6 mA or higher.

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Surgical management of cerebellopontine angle epidermoid cysts: an institutional experience of 10 years

BRITISH JOURNAL OF NEUROSURGERY 2022, VOL. 36, NO. 2, 203–212

Cerebellopontine angle (CPA) epidermoids, although of benign nature, are of considerable neurosurgical interest because of their close proximity and adherence to the cranial nerves and brain stem. In this paper, we describe our experience and attempt to correlate the final outcomes with the extent of surgical removal. The main objectives were to study various modes of surgical management of CPA epidermoids with regard to removal and preservation of the cranial nerves and also to evaluate the role of endoscopic assisted microsurgical excision thereby minimizing recurrences. This case series is one of the largest series reported so far worldwide.

Materials and methods: From 2006 to 2016, 139 patients with CPA epidermoids were operated at Grant Medical College and J. J. Hospital, Mumbai. All patients underwent detailed magnetic resonance imaging (MRI) of brain. Lesions were classified according Rogelio Revuelta-Gutierrez et al. with respect to their anatomic extent: grade I- within the boundaries of the CPA, grade II- extension to the suprasellar and perimesencephalic cisterns, and grade III-parasellar and temporomesial region involvement. Retrosigmoidal and subtemporal approaches were taken to excise the lesions. Endoscopic assisted microsurgical excision was done in cases with extensions beyond the CPA. Patient follow-up was based on outpatient repeated brain MRI studies.

Results: The mean duration of symptoms before surgery was 42 months (range, 2 months to 6 years). The mean follow-up period was 27 months (range, 2–60 months). The main presenting symptom was headache in 69% (96/139) of the cases and trigeminal neuralgia in 30% cases was the second most common cause of consultation. Seventy-five percent of patients had some degree of cranial nerve (CN) involvement. Retrosigmoid approach was taken in 92% patients and 7 patients with supratentorial extension were operated by combined retrosigmoidal and subtemporal approach. Endoscopic assisted microsurgical excision was done in 40% cases. Use of angled views by an endoscope helped to excise residual tumor in 47 (83%) patients. Complete excision was achieved in 67% of cases. In 33% patients, small capsular remnants could not be removed completely because of their adherence to vessels, brainstem and cranial nerves. Compared with their preoperative clinical status, 74% improved and 20% had persistent cranial nerve deficits in the first year of follow up.

Conclusions: Epidermoid cysts are challenging entities in current neurosurgery practice due to tumor adhesions to neurovascular structures. Meticulous surgical technique with the aid of neurophysiological monitoring is crucial to achieve safe and effective total or subtotal removal of these lesions. A conservative approach is indicated for patients in whom the fragments of capsule is adhered closely to blood vessels, nerves, or the brainstem, in order to avoid risk of serious neurological deficits related to an inadvertent damage of these structures. Use of angled views by endoscope at the conclusion of the surgery may assure the surgeon of total removal of the tumor.

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Review of Cerebrospinal Fluid Physiology and Dynamics: A Call for Medical Education Reform

Neurosurgery 91:1–7, 2022

The flow of cerebrospinal fluid (CSF) has been described as a unidirectional system with the choroid plexus serving as the primary secretor of CSF and the arachnoid granulations as primary reabsorption site. This theory of neurosurgical forefathers has been universally adopted and taught as dogma. Many neuroscientists have found difficulty reconciling this theory with common pathologies, and recent studies have found that this “classic” hypothesis may not represent the full picture.

OBJECTIVE: To review modern CSF dynamic theories and to call formedical education reform.

METHODS: We reviewed the literature from January 1990 to December 2020. We searched the PubMed database using key terms “cerebrospinal fluid circulation,” “cerebrospinal fluid dynamics,” “cerebrospinal fluid physiology,” “glymphatic system,” and “glymphatic pathway.” We selected articles with a primary aim to discuss either CSF dynamics and/or the glymphatic system.

RESULTS: The Bulat–Klarica–Oreˇskovi´c hypothesis purports that CSF is secreted and reabsorbed throughout the craniospinal axis. CSF demonstrates similar physiology to that of water elsewhere in the body. CSF “circulates” throughout the subarachnoid space in a pulsatile to-and-fro fashion. Osmolarity plays a critical role in CSF dynamics. Aquaporin-4 and the glymphatic system contribute to CSF volume and flow by establishing osmolarity gradients and facilitating CSF movement. Multiple studies demonstrate that the choroid plexus does not play any significant role in CSF circulation.

CONCLUSION: We have highlighted major studies to illustrate modern principles of CSF dynamics. Despite these, the medical education system has been slow to reform curricula and update learning resources.

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Cerebrospinal fluid and venous biomarkers of shunt‐responsive idiopathic normal pressure hydrocephalus: a systematic review and meta‐analysis

Acta Neurochirurgica (2022) 164:1719–1746

Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease and dementia subtype involving disturbed cerebrospinal fluid (CSF) homeostasis. Patients with iNPH may improve clinically following CSF diversion through shunt surgery, but it remains a challenge to predict which patients respond to shunting. It has been proposed that CSF and blood biomarkers may be used to predict shunt response in iNPH.

Objective To conduct a systematic review and meta-analysis to identify which CSF and venous biomarkers predict shunt- responsive iNPH most accurately.

Methods Original studies that investigate the use of CSF and venous biomarkers to predict shunt response were searched using the following databases: Embase, MEDLINE, Scopus, PubMed, Google Scholar, and JSTOR. Included studies were assessed using the ROBINS-I tool, and eligible studies were evaluated utilising univariate meta-analyses.

Results The study included 13 studies; seven addressed lumbar CSF levels of amyloid-β 1–42, nine studies CSF levels of Total-Tau, six studies CSF levels of Phosphorylated-Tau, and seven studies miscellaneous biomarkers, proteomics, and genotyping. A meta-analysis of six eligible studies conducted for amyloid-β 1–42, Total-Tau, and Phosphorylated-Tau demonstrated significantly increased lumbar CSF Phosphorylated-Tau (− 0.55 SMD, p = 0.04) and Total-Tau (− 0.50 SMD, p = 0.02) in shunt-non-responsive iNPH, though no differences were seen between shunt responders and non-responders for amyloid-β 1–42 (− 0.26 SMD, p = 0.55) or the other included biomarkers.

Conclusion This meta-analysis found that lumbar CSF levels of Phosphorylated-Tau and Total-Tau are significantly increased in shunt non-responsive iNPH compared to shunt-responsive iNPH. The other biomarkers, including amyloid-β 1–42, did not significantly differentiate shunt-responsive from shunt-non-responsive iNPH. More studies on the Tau proteins examining sensitivity and specificity at different cut-off levels are needed for a robust analysis of the diagnostic efficiency of the Tau proteins.

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The impact of multiple lesions on progression-free survival of meningiomas: a 10-year multicenter experience

J Neurosurg 137:9–17, 2022

Multiple meningiomas (MMs) occur in as many as 18% of patients with meningioma, and data on progression- free survival (PFS) are scarce. The objective of this study was to explore the influence of the number of lesions and clinical characteristics on PFS in patients with WHO grade I meningiomas.

METHODS The authors retrospectively reviewed the records of all adults diagnosed with a meningioma at their three main sites from January 2009 to May 2020. Progression was considered the time from diagnosis until radiographic growth of the originally resected meningioma. A secondary analysis was performed to evaluate the time of diagnosis until the time to second intervention (TTSI). Univariable and multivariable analyses were conducted to assess whether the number of lesions or any associated variables (age, sex, race, radiation treatment, tumor location, and extent of resection) had a significant impact on PFS and TTSI.

RESULTS Eight hundred thirty-eight patients were included. Use of a log-rank test to evaluate PFS and TTSI between a single and multiple lesions showed a significantly shorter progression for MM (p < 0.001 and p < 0.001, respectively). Multivariable Cox regression analysis showed significantly inferior PFS on MM compared to a single lesion (hazard ratio [HR] 2.262, 95% confidence interval [CI] 1.392–3.677, p = 0.001) and a significantly inferior TTSI for patients with MM when compared to patients with a single meningioma (HR 2.377, 95% CI 1.617–3.494, p = 0.001). By testing the number of meningiomas as a continuous variable, PFS was significantly inferior for each additional meningioma (HR 1.350, 95% CI 1.074–1.698, p = 0.010) and TTSI was significantly inferior as well (HR 1.428, 95% CI 1.189–1.716, p < 0.001). African American patients had an inferior PFS when compared to non-Hispanic White patients (HR 3.472, 95% CI 1.083–11.129, p = 0.036).

CONCLUSIONS The PFS of meningiomas appears to be influenced by the number of lesions present. Patients with MM also appear to be more prone to undergoing a second intervention for progressive disease. Hence, a closer follow-up may be warranted in patients who present with multiple lesions. These results show a decreased PFS for each additional lesion present, as well as a shorter PFS for MM compared to a single lesion. When assessing associated risk factors, African American patients showed an inferior PFS, whereas older age and adjuvant therapy with radiation showed an improved PFS.

 

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Internal Carotid Artery Classification Systems: An Illustrative Review

World Neurosurg. (2022) 163:41-49

The internal carotid artery (ICA) course has been discussed extensively. Several classification systems have attempted to delineate an accurate and helpful trajectory for microsurgical and endoscopic guidance, thus allowing a better neurosurgical performance while avoiding intraoperative complications. Also, the practicality of the classification systems has been emphasized for scholarly communication among disciplines. Nevertheless, the nomenclature of the ICA remains heterogeneous and confusing for health care professionals, trainees, and students.

We present an illustrative review of 8 notable ICA classification systems using lateral and anterior views as a rapid tool for neuroanatomic consultation. The appraisal of the vessel anatomy from different perspectives while recognizing their usefulness and limitations might provide a comprehensive understanding of the ICA, optimize the intraoperative performance, and facilitate communication

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Safe Electromyography Stimulation Thresholds Within Kambin’s Triangle During Endoscopic Transforaminal Lumbar Interbody Fusion

Neurosurgery 91:150–158, 2022

Transforaminal endoscopic approaches through Kambin’s triangle traditionally require surgery to be performed without general anesthesia to allow live patient feedback. No reliable intraoperative neuromonitoring method specific to the dorsal root ganglion (DRG), the structure most at risk during this approach, currently exists.

OBJECTIVE: To correlate evoked electromyography (EMG) thresholds within Kambin’s triangle with new postoperative pain or sensorimotor symptoms potentially resulting from DRG irritation.

METHODS: Data were prospectively collected for all patients undergoing endoscopic transforaminal lumbar interbody fusion (TLIF) under general anesthesia at a single institution. A stimulation probe was inserted into Kambin’s triangle under fluoroscopic and robotic guidance, before passage of endoscopic instruments. EMG thresholds required to elicit corresponding myotomal responses were measured. Postoperatively, any potential manifestations of DRG irritation were recorded.

RESULTS: Twenty-four patients underwent a total of 34 transforaminal lumbar interbody fusion levels during the study period, with symptoms of potential DRG irritation occurring in 5. The incidence of new onset symptoms increased with lower stimulation thresholds. Sensitivities for EMG thresholds of ≤4, ≤8, and ≤11 mA were 0.6, 0.8, and 1, respectively. Corresponding specificities were 0.90, 0.69, and 0.55, respectively.

CONCLUSION: We demonstrated for the first time the feasibility of direct intraoperative neuromonitoring within Kambin’s triangle in transforaminal endoscopic surgery. Eight milliampere seems to be a reasonable compromise between sensitivity and specificity for this monitoring technique. In the future, larger-scale studies are required to refine safe stimulation thresholds.

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