Nonoperative versus operative management of type II odontoid fracture in older adults: a systematic review and meta-analysis

J Neurosurg Spine 40:45–53, 2024

Odontoid fractures are the most common fracture of the cervical spine in adults older than 65 years of age. Fracture management remains controversial, given the inherently increased surgical risks in older patients. The objective of this study was to compare fusion rates and outcomes between operative and nonoperative treatments of type II odontoid fractures in the older population.

METHODS A systematic literature review was performed to identify studies reporting the management of type II odontoid fractures in patients older than 65 years from database inception to September 2022. A meta-analysis was performed to compare rates of fusion, stable and unstable nonunion, mortality, and complication.

RESULTS Forty-six articles were included in the final review. There were 2822 patients included in the different studies (48.9% female, 51.1% male), with a mean ± SD age of 81.5 ± 3.6 years. Patients in the operative group were significantly younger than patients in the nonoperative group (81.5 ± 3.5 vs 83.4 ± 2.5 years, p < 0.001). The overall (operative and nonoperative patients) fusion rate was 52.9% (720/1361). The fusion rate was higher in patients who underwent surgery (74.3%) than in those who underwent nonoperative management (40.3%) (OR 4.27, 95% CI 3.36–5.44). The likelihood of stable or unstable nonunion was lower in patients who underwent surgery (OR 0.37, 95% CI 0.28–0.49 vs OR 0.32, 95% CI 0.22–0.47). Overall, 4.8% (46/964) of nonoperatively managed patients subsequently required surgery due to treatment failure. Patient mortality across all studies was 16.6% (452/2721), lower in the operative cohort (13.2%) than the nonoperative cohort (19.0%) (OR 0.64, 95% CI 0.52–0.80). Complications were more likely in patients who underwent surgery (26.0% vs 18.5%) (OR 1.55, 95% CI 1.23–1.95). Length of stay was also higher with surgery (13.6 ± 3.8 vs 8.1 ± 1.9 days, p < 0.001).

CONCLUSIONS Patients older than 65 years of age with type II odontoid fractures had higher fusion rates when treated with surgery and higher stable nonunion rates when managed nonoperatively. Complications and length of stay were higher in the surgical cohort. Mortality rates were lower in patients managed with surgery, but this phenomenon could be related to surgical selection bias. Fewer than 5% of patients who underwent nonoperative treatment required revision surgery due to treatment failure, suggesting that stable nonunion is an acceptable treatment goal.

Awake Versus Asleep Craniotomy for Patients With Eloquent Glioma: A Systematic Review and Meta-Analysis

Neurosurgery 94:38–52, 2024

Awake vs asleep craniotomy for patients with eloquent glioma is debatable. This systematic review and meta-analysis sought to compare awake vs asleep craniotomy for the resection of gliomas in the eloquent regions. METHODS: MEDLINE and PubMed were searched from inception to December 13, 2022. Primary outcomes were the extent of resection (EOR), overall survival (month), progression-free survival (month), and rates of neurological deficit, Karnofsky performance score, and seizure freedom at the 3-month follow-up. Secondary outcomes were duration of operation (minute) and length of hospital stay (LOS) (day).

RESULTS: Fifteen studies yielded 2032 patients, from which 800 (39.4%) and 1232 (60.6%) underwent awake and asleep craniotomy, respectively. The meta-analysis concluded that the awake group had greater EOR (mean difference [MD]= MD= 8.52 [4.28, 12.76], P < .00001), overall survival (MD = 2.86 months [1.35, 4.37], P = .0002), progression-free survival (MD = 5.69 months [0.75, 10.64], P = .02), 3-month postoperative Karnofsky performance score (MD = 13.59 [11.08, 16.09], P < .00001), and 3-month postoperative seizure freedom (odds ratio = 8.72 [3.39, 22.39], P < .00001). Furthermore, the awake group had lower 3-month postoperative neurological deficit (odds ratio = 0.47 [0.28, 0.78], P = .004) and shorter LOS (MD = -2.99 days [-5.09, -0.88], P = .005). In addition, the duration of operation was similar between the groups (MD = 37.88 minutes [-34.09, 109.86], P = .30).

CONCLUSION: Awake craniotomy for gliomas in the eloquent regions benefits EOR, survival, postoperative neurofunctional outcomes, and LOS. When feasible, the authors recommend awake craniotomy for surgical resection of gliomas in the eloquent regions.

Modic Changes Increase the Cage Subsidence Rate in Spinal Interbody Fusion Surgery: A Systematic Review and Network Meta-Analysis

OBJECTIVE: To compare the effect of different Modic changes (MC) grades on the cage subsidence rate after spinal interbody fusion surgery.

METHODS: We comprehensively searched the PubMed, Embase, and Web of Science databases from inception to August 13, 2023, for relevant randomized controlled trials and prospective and retrospective cohort studies. Review Manager 5.3 and STATA13.0 were used to conduct this meta-analysis. The subsidence rate was assessed using relative risk and 95% confidence intervals.

RESULTS: Six studies with a total of 716 segments were allocated to four groups according to the type of MC. The subsidence rate in the non-Modic changes (NMC) was significantly lower than that in the MC. The subsidence rate in the NMC was significantly lower than that in the MC in the subgroup of cages with extra instrumentation. No significant difference was identified between the 2 groups in the oblique lumbar interbody fusion subgroup. The subsidence rate in the NMC was significantly lower than that in the MC in the transforaminal lumbar interbody fusion subgroup. The subsidence rate in the NMC was significantly lower than that in the MC1 and MC2. We found no significant difference between NMC and MC3, MC1 and MC2, MC1 and MC3, or MC2 and MC3.

CONCLUSIONS: MC may be associated with a higher cage subsidence rate. With the increase in MC grades, the incidence of subsidence decreased gradually, but it was always higher than that in the NMC. Oblique lumbar interbody fusion may be a better choice for the treatment of lumbar degenerative disease with MC.

Optimizing surgical management of facet cysts of the lumbar spine: systematic review, meta-analysis, and local case series of 1251 patients

J Neurosurg Spine 39:793–806, 2023

Lumbar facet cysts (LFCs) can cause neurological dysfunction and intractable pain. Surgery is the current standard of care for patients in whom conservative therapy fails, those with neurological deficits, and those with evidence of spinal instability. No study to date has comprehensively examined surgical outcomes comparing the multiple surgical treatment options for LFCs. Therefore, the authors aimed to perform a combined analysis of cases both in the literature and of patients at a single institution to compare the outcomes of various surgical treatment options for LFC.

METHODS The authors performed a literature review in accordance with PRISMA guidelines and meta-analysis of the PubMed, Embase, and Cochrane Library databases and reviewed all studies from database inception published until February 3, 2023. Studies that did not contain 3 or more cases, clearly specify follow-up durations longer than 6 months, or present new cases were excluded. Bias was evaluated using Cochrane Collaboration’s Risk of Bias in Nonrandomised Studies–of Interventions (ROBINS-I). The authors also reviewed their own local institutional case series from 2015 to 2020. Primary outcomes were same-level cyst recurrence, same-level revision surgery, and perioperative complications. ANOVA, common and random-effects modeling, and Wald testing were used to compare treatment groups.

RESULTS A total of 1251 patients were identified from both the published literature (29 articles, n = 1143) and the authors’ institution (n = 108). Patients were sorted into 5 treatment groups: open cyst resection (OCR; n = 720), tubular cyst resection (TCR; n = 166), cyst resection with arthrodesis (CRA; n = 165), endoscopic cyst resection (ECR; n = 113), and percutaneous cyst rupture (PCR; n = 87), with OCR being the analysis reference group. The PCR group had significantly lower complication rates (p = 0.004), higher recurrence rates (p < 0.001), and higher revision surgery rates (p = 0.001) compared with the OCR group. Patients receiving TCR (3.01%, p = 0.021) and CRA (0.0%, p < 0.001) had significantly lower recurrence rates compared with those undergoing OCR (6.36%). The CRA group (6.67%) also had significantly lower rates of revision surgery compared with the OCR group (11.3%, p = 0.037).

CONCLUSIONS While PCR is less invasive, it may have high rates of same-level recurrence and revision surgery. Recurrence and revision rates for modalities such as ECR were not significantly different from those of OCR. While concomitant arthrodesis is more invasive, it might lead to lower recurrence rates and lower rates of subsequent revision surgery. Given the limitations of our case series and literature review, prospective, randomized studies are needed.

Effect of Lumbar Discectomy or Lumbar Decompression on Axial Back Pain: Results of a Meta-Analysis

World Neurosurg. (2023) 177:109-121

This meta-analysis evaluated the impact of lumbar disk herniation and lumbar spinal stenosis (LSS) on axial back pain and the extent of improvement of axial and radicular pain following lumbar decompression and discectomy surgery in patients with low back pain (LBP).

METHODS: A systematic search for published literature between January 2012 and January 2023 was made on PubMed, Google Scholar, and Cochrane library database on 31 st January 2023.

Original articles that included patients with lumbar disc herniation or LSS who underwent lumbar discectomy or lumbar decompression respectively were included in the study.

RESULTS: A total of 71 studies including 16,770 patients with LBP undergoing lumbar discectomy or decompression surgery were included in the metaanalysis. The pooled standard mean difference between postoperative and preoperative: Visual Analog Scale scores for leg pain was L5.14 with 95% confidence interval (CI): L6.59 to L3.69 (P-value [ 0) and for back pain was L2.90 with 95% CI: L3.79 to L2.01 (P value [ 0), Numerical pain Rating Scale for leg pain was L1.64 with 95% CI: L1.97 to L1.30 (P-value<0.01) and for back pain was L1.58 with 95% CI: L1.84 to L1.32 (P-value <0.01), Oswerty Disability Index score was L4.76 with 95% CI: L6.22 to L3.29 (P-value [ 0) and the Japanese Orthopaedic Association score was 3.45 with 95% CI: 0.02 to 6.88 (P value 0) at follow-up.

CONCLUSIONS: This meta-analysis provides evidence that lumbar discectomy and decompression are effective in improving axial LBP in patients with lumbar disk herniation and LSS.


A Systematic Review Comparing Focused Ultrasound Surgery With Radiosurgery for Essential Tremor

Neurosurgery 93:524–538, 2023

Focused ultrasound (FUS-T) and stereotactic radiosurgery thalamotomy (SRS-T) targeting the ventral intermediate nucleus are effective incisionless surgeries for essential tremor (ET). However, their efficacy for tremor reduction and, importantly, adverse event incidence have not been directly compared.

OBJECTIVE: To present a comprehensive systematic review with network meta-analysis examining both efficacy and adverse events (AEs) of FUS-T vs SRS-T for treating medically refractory ET.

METHODS: We conducted a systematic review and network meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using the PubMed and Embase databases. We included all primary FUS-T/SRS-T studies with approximately 1-year follow-up, with unilateral Fahn-Tolosa-Marin Tremor Rating Scale or Clinical Rating Scale for Tremor scores prethalamotomy/post-thalamotomy and/or AEs. The primary efficacy outcome was Fahn-Tolosa-Marin Tremor Rating Scale A+B score reduction. AEs were reported as an estimated incidence.

RESULTS: Fifteen studies of 464 patients and 3 studies of 62 patients met inclusion criteria for FUS-T/SRS-T efficacy comparison, respectively. Network meta-analysis demonstrated similar tremor reduction between modalities (absolute tremor reduction: FUS-T: À11.6 (95% CI: À13.3, À9.9); SRS-T: À10.3 (95% CI: À14.2, À6.0). FUS-T had a greater 1-year adverse event rate, particularly imbalance and gait disturbances (10.5%) and sensory disturbances (8.3%). Contralateral hemiparesis (2.7%) often accompanied by speech impairment (2.4%) were most common after SRS-T. There was no correlation between efficacy and lesion volume.

CONCLUSION: Our systematic review found similar efficacy between FUS-T and SRS-T for ET, with trend toward higher efficacy yet greater adverse event incidence with FUS-T. Smaller lesion volumes could mitigate FUS-T off-target effects for greater safety.

Outcomes following anterior odontoid screw versus posterior arthrodesis for odontoid fractures

J Neurosurg Spine 39:196–205, 2023

Odontoid fractures can be managed surgically when indicated. The most common approaches are anterior dens screw (ADS) fixation and posterior C1–C2 arthrodesis (PA). Each approach has theoretical advantages, but the optimal surgical approach remains controversial. The goal in this study was to systematically review the literature and synthesize outcomes including fusion rates, technical failures, reoperation, and 30-day mortality associated with ADS versus PA for odontoid fractures.

METHODS A systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines by searching the PubMed, EMBASE, and Cochrane databases. A random-effects meta-analysis was performed and the I 2 statistic was used to assess heterogeneity.

RESULTS In total, 22 studies comprising 963 patients (ADS 527, PA 436) were included. The average age of the patients ranged from 28 to 81.2 years across the included studies. The majority of the odontoid fractures were type II based on the Anderson-D’Alonzo classification. The ADS group was associated with statistically significantly lower odds to achieve bony fusion at last follow-up compared to the PA group (ADS 84.1%; PA 92.3%; OR 0.46; 95% CI 0.23–0.91; I 2 42.6%). The ADS group was associated with statistically significantly higher odds of reoperation compared to the PA group (ADS 12.4%; PA 5.2%; OR 2.56; 95% CI 1.50–4.35; I 2 0%). The rates of technical failure (ADS 2.3%; PA 1.1%; OR 1.11; 95% CI 0.52–2.37; I 2 0%) and all-cause mortality (ADS 6%; PA 4.8%; OR 1.35; 95% CI 0.67–2.74; I 2 0%) were similar between the two groups. In the subgroup analysis of patients > 60 years old, the ADS was associated with statistically significantly lower odds of fusion compared to the PA group (ADS 72.4%; PA 89.9%; OR 0.24; 95% CI 0.06–0.91; I 2 58.7%).

CONCLUSIONS ADS fixation is associated with statistically significantly lower odds of fusion at last follow-up and higher odds of reoperation compared to PA. No differences were identified in the rates of technical failure and all-cause mortality. Patients receiving ADS fixation at > 60 years old had significantly higher and lower odds of reoperation and fusion, respectively, compared to the PA group. PA is preferred to ADS fixation for odontoid fractures, with a stronger effect size for patients > 60 years old.

Internal Ventricular Cerebrospinal Fluid Shunt for Adult Hydrocephalus: A Systematic Review and Meta-Analysis of the Infection Rate

Hydrocephalus is a common neurological condition that usually requires internal ventricular cerebrospinal fluid shunt (IVCSFS). The reported infection rate (IR) varies greatly from below 1% up to over 50%, but no meta-analysis to assess the overall IR has ever been performed.

OBJECTIVE: To determine the IVCSFS overall IR in the adult population and search for associated factors.

METHODS: Six databases were searched from January 1990 to July 2022. Only original articles reporting on adult IVCSFS IR were included. Random-effects meta-analysis with generalized linear mixed model method and logit transformation was used to assess the overall IR. RESULTS: Of 1703 identified articles, 44 were selected, reporting on 57259 patients who had IVCSFS implantation and 2546 infections. The pooled IR value and its 95% CI were 4.75%, 95% CI (3.8 to 5.92). Ninety-five percent prediction interval ranged from 1.19% to 17.1%. The patients who had IVCSFS after intracranial hemorrhage showed a higher IR (7.65%, 95% CI [5.82 to 10], P-value = .002). A meta-regression by year of publication found a decreasing IR (À0.031, 95% CI [À0.06 to 0.003], P-value = .032) over the past 32 years.

CONCLUSION: IVCSF is a procedure that every neurosurgeon should be well trained to perform. However, the complication rate remains high, with an estimated overall IR of 4.75%. The IR is especially elevated for hydrocephalic patients who require IVCSFS after intracranial hemorrhage. However, decades of surgical advances may have succeeded in reducing IR over the past 32 years.

Neurosurgery 92:894–904, 2023

Sacrifice or preserve the superior petrosal vein in microvascular decompression surgery

J Neurosurg 138:390–398, 2023

In microvascular decompression (MVD) surgery through the retrosigmoid approach, the surgeon may have to sacrifice the superior petrosal vein (SPV). However, this is a controversial maneuver. To date, high-level evidence comparing the operative outcomes of patients who underwent MVD with and without SPV sacrifice is lacking. Therefore, this study sought to bridge this gap.

METHODS The authors searched the Medline and PubMed databases with appropriate Medical Subject Heading (MeSH) terms and keywords. The primary outcome was vascular-related complications; secondary outcomes were new neurological deficit, cerebrospinal fluid (CSF) leak, and neuralgia relief. The pooled proportions of outcomes and OR (95% CI) for categorical data were calculated by using the logit transformation and Mantel-Haenszel methods, respectively.

RESULTS Six studies yielding 1143 patients were included, of which 618 patients had their SPV sacrificed. The pooled proportion (95% CI) values were 3.82 (0.87–15.17) for vascular-related complications, 3.64 (1.0–12.42) for new neurological deficits, 2.85 (1.21–6.58) for CSF leaks, and 88.90 (84.90–91.94) for neuralgia relief. The meta-analysis concluded that, whether the surgeon sacrificed or preserved the SPV, the odds were similar for vascular-related complications (2.5% vs 1.5%, OR [95% CI] 1.01 [0.33–3.09], p = 0.99), new neurological deficits (1.2% vs 2.8%, OR [95% CI] 0.55 [0.18–1.66], p = 0.29), CSF leak (3.1% vs 2.1%, OR [95% CI] 1.16 [0.46–2.94], p = 0.75), and neuralgia relief (86.6% vs 87%, OR [95% CI] 0.96 [0.62–1.49], p = 0.84).

CONCLUSIONS SPV sacrifice is as safe as SPV preservation. The authors recommend intentional SPV sacrifice when gentle retraction fails to enhance surgical field visualization and if the surgeon encounters SPV-related neurovascular conflict and/or anticipates impeding SPV-related bleeding.


Predictors for cervical kyphotic deformity following laminoplasty: a systematic review and meta-analysis

J Neurosurg Spine 38:4–13, 2023

Laminoplasty is a common treatment for cervical spondylotic myelopathy (CSM) and for ossification of the posterior longitudinal ligament (OPLL). However, approximately 21% of patients undergoing laminoplasty develop cervical kyphotic deformity (KD). Because of the high prevalence rate of KD, several studies have sought to identify predictors for this complication, but the findings remain highly inconsistent. Therefore, the authors performed a systematic review and meta-analysis to establish reliable preoperative predictors of KD.

METHODS PubMed, Scopus, and Web of Science databases were used to systematically extract potential references. The first phase of screening required the studies to be written in the English language, involve patients treated for CSM and/or OPLL via laminoplasty, and report postoperative cervical KD. The second phase required the studies to provide more than 10 patients and include a control group. The mean difference (MD) and odds ratio (OR) were calculated for continuous and dichotomous parameters. Study quality was evaluated using the Newcastle-Ottawa Scale. CSM and OPLL patients were further assessed by performing subgroup analyses.

RESULTS Thirteen studies comprising patients who developed cervical KD (n = 296) and no KD (n = 1254) after receiving cervical laminoplasty for CSM or OPLL were included in the meta-analysis. All studies were retrospective cohorts and were rated as high quality. In the combined univariate analysis of CSM and OPLL patients undergoing laminoplasty, statistically significant predictors for postoperative KD included age (MD 2.22, 95% CI 0.16–4.27, p = 0.03), preoperative BMI (MD 0.85, 95% CI 0.06–1.63, p = 0.04), preoperative C2–7 range of flexion (MD 10.42, 95% Cl 4.24–16.59, p = 0.0009), preoperative C2–7 range of extension (MD −4.59, 95% CI −6.34 to −2.83, p < 0.00001), and preoperative center of gravity of the head to the C7 sagittal vertical axis (MD 26.83, 95% CI 9.13–44.52, p = 0.003). Additionally, among CSM patients, males were identified as having a greater risk for postoperative KD (OR 1.73, 95% CI 1.02–2.93, p = 0.04).

CONCLUSIONS The findings from this study currently provide the largest and most reliable review on preoperative predictors for cervical KD after laminoplasty. Given that several of the included studies identified optimal cutoff points for the variables that are significantly associated with KD, further investigation into the development of a preoperative risk scoring system that can accurately predict KD in the clinical setting is encouraged.

Stereotactic Radiosurgery for A Randomized Trial of Unruptured Brain Arteriovenous Malformations- Eligible Patients: A Meta-Analysis

Neurosurgery 91:684–692, 2022

The outcomes of A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) were controversial, and they suggested that intervention is inferior to medical management for unruptured brain arteriovenous malformations (AVMs). However, several studies have shown that stereotactic radiosurgery (SRS) is an acceptable therapy for unruptured AVMs.

OBJECTIVE: To test the hypothesis that ARUBA intervention arm’s SRS results are meaningfully inferior to those from similar populations reported by other studies.

METHODS: We performed a literature review to identify SRS studies of patients who met the eligibility criteria for ARUBA. Patient, AVM, treatment, and outcome data were extracted for statistical analysis. Regression analyses were pooled to identify factors associated with post-SRS obliteration and hemorrhage.

RESULTS: The study cohort included 8 studies comprising 1620 ARUBA-eligible patients who underwent SRS. At the time of AVM diagnosis, 36% of patients were asymptomatic. The mean follow-up duration was 80 months. Rates of radiologic, symptomatic, and permanent radiation-induced changes were 45%, 11%, and 2%, respectively. The obliteration rate was 68% at last follow-up. The post-SRS hemorrhage and mortality rates were 8%, and 2%, respectively. Lower Spetzler-Martin grade (odds ratios [OR] = 0.84 [0.74-0.95], P = .005), lower radiosurgery-based AVM score (OR = 0.75 [0.64-0.95], P = .011), lower Virginia Radiosurgery AVM Scale (OR = 0.86 [0.78-0.95], P = .003), and higher margin dose (OR = 1.13 [1.02-1.25], P = .025) were associated with obliteration.

CONCLUSION: SRS carries a favorable risk to benefit profile for appropriately selected ARUBA-eligible patients, particularly those with smaller volume AVMs. Our findings suggest that the results of ARUBA do not reflect the real-world safety and efficacy of SRS for unruptured AVMs.

Prevalence of incidental intracranial findings on magnetic resonance imaging: a systematic review and meta‑analysis

Acta Neurochirurgica (2022) 164:2751–2765

As the volume and fidelity of magnetic resonance imaging (MRI) of the brain increase, observation of incidental findings may also increase. We performed a systematic review and meta-analysis to determine the prevalence of various incidental findings.

Methods PubMed/MEDLINE, EMBASE and SCOPUS were searched from inception to May 24, 2021. We identified 6536 citations and included 35 reports of 34 studies, comprising 40,777 participants. A meta-analysis of proportions was performed, and age-stratified estimates for each finding were derived from age-adjusted non-linear models.

Results Vascular abnormalities were observed in 423/35,706 participants (9.1/1000 scans, 95%CI 5.2–14.2), ranging from 2/1000 scans (95%CI 0–7) in 1-year-olds to 16/1000 scans (95%CI 1–43) in 80-year-olds. Of these, 204/34,306 were aneurysms (3.1/1000 scans, 95%CI 1–6.3), which ranged from 0/1000 scans (95%CI 0–5) at 1 year of age to 6/1000 scans (95%CI 3–9) at 60 years. Neoplastic abnormalities were observed in 456/39,040 participants (11.9/1000 scans, 95%CI 7.5–17.2), ranging from 0.2/1000 scans (95%CI 0–10) in 1-year-olds to 34/1000 scans (95%CI 12–66) in 80-year-olds. Meningiomas were the most common, in 246/38,076 participants (5.3/1000 scans, 95%CI 2.3–9.5), ranging from 0/1000 scans (95%CI 0–2) in 1-year-olds to 17/1000 scans (95%CI 4–37) in 80-year-olds. Chiari malformations were observed in 109/27,408 participants (3.7/1000 scans, 95%CI 1.8–6.3), pineal cysts in 1176/32,170 (9/1000 scans, 95%CI 1.8–21.4) and arachnoid cysts in 414/36,367 (8.5/1000 scans, 95%CI 5.8–11.8).

Conclusion Incidental findings are common on brain MRI and may result in substantial resource expenditure and patient anxiety but are often of little clinical significance.

Comparison of anterior cervical discectomy and fusion versus artificial disc replacement for cervical spondylotic myelopathy: a meta-analysis

J Neurosurg Spine 37:569–578, 2022

Anterior cervical discectomy and fusion (ACDF) has long been regarded as a gold standard in the treatment of cervical myelopathy. Subsequently, cervical artificial disc replacement (c-ADR) was developed and provides the advantage of motion preservation at the level of the intervertebral disc surgical site, which may also reduce stress at adjacent levels. The goal of this study was to compare clinical and functional outcomes in patients undergoing ACDF with those in patients undergoing c-ADR for cervical spondylotic myelopathy (CSM).

METHODS A systematic literature review and meta-analysis were performed using the Embase, PubMed, and Cochrane Central Register of Controlled Trials databases from database inception to November 21, 2021. The authors compared Neck Disability Index (NDI), SF-36, and Japanese Orthopaedic Association (JOA) scores; complication rates; and reoperation rates for these two surgical procedures in CSM patients. The Mantel-Haenszel method and varianceweighted means were used to analyze outcomes after identifying articles that met study inclusion criteria.

RESULTS More surgical time was consumed in the c-ADR surgery (p = 0.04). Shorter hospital stays were noted in patients who had undergone c-ADR (p = 0.04). Patients who had undergone c-ADR tended to have better NDI scores (p = 0.02) and SF-36 scores (p = 0.001). Comparable outcomes in terms of JOA scores (p = 0.24) and neurological success rate (p = 0.12) were noted after the surgery. There was no significant between-group difference in the overall complication rates (c-ADR: 18% vs ACDF: 25%, p = 0.17). However, patients in the ACDF group had a higher reoperation rate than patients in the c-ADR group (4.6% vs 1.5%, p = 0.02).

CONCLUSIONS At the midterm follow-up after treatment of CSM, better functional outcomes as reflected by NDI and SF-36 scores were noted in the c-ADR group than those in the ACDF group. c-ADR had the advantage of retaining range of motion at the level of the intervertebral disc surgical site without causing more complications. A large sample size with long-term follow-up studies may be required to confirm these findings in the future.

Robot-assisted and augmented reality–assisted spinal instrumentation

J Neurosurg Spine 37:299–314, 2022

The use of technology-enhanced methods in spine surgery has increased immensely over the past decade. Here, the authors present the largest systematic review and meta-analysis to date that specifically addresses patient-centered outcomes, including the risk of inaccurate screw placement and perioperative outcomes in spinal surgeries using robotic instrumentation and/or augmented reality surgical navigation (ARSN).

METHODS A systematic review of the literature in the PubMed, EMBASE, Web of Science, and Cochrane Library databases spanning the last decade (January 2011–November 2021) was performed to present all clinical studies comparing robot-assisted instrumentation and ARSN with conventional instrumentation techniques in lumbar spine surgery. The authors compared these two technologies as they relate to screw accuracy, estimated blood loss (EBL), intraoperative time, length of stay (LOS), perioperative complications, radiation dose and time, and the rate of reoperation.

RESULTS A total of 64 studies were analyzed that included 11,113 patients receiving 20,547 screws. Robot-assisted instrumentation was associated with less risk of inaccurate screw placement (p < 0.0001) regardless of control arm approach (freehand, fluoroscopy guided, or navigation guided), fewer reoperations (p < 0.0001), fewer perioperative complications (p < 0.0001), lower EBL (p = 0.0005), decreased LOS (p < 0.0001), and increased intraoperative time (p = 0.0003). ARSN was associated with decreased radiation exposure compared with robotic instrumentation (p = 0.0091) and fluoroscopy-guided (p < 0.0001) techniques.

CONCLUSIONS Altogether, the pooled data suggest that technology-enhanced thoracolumbar instrumentation is advantageous for both patients and surgeons. As the technology progresses and indications expand, it remains essential to continue investigations of both robotic instrumentation and ARSN to validate meaningful benefit over conventional instrumentation techniques in spine surgery.

Systematic review registration no.: CRD42021283631 (

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

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.

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.

Effect of topical and intraventricular antibiotics used during ventriculoperitoneal shunt insertion on the rate of shunt infection—a meta‐analysis

Acta Neurochirurgica (2022) 164:1793–1803

The ventriculoperitoneal shunt is one of the most commonly performed neurosurgical procedures. One of the avoidable complications of shunt surgery is shunt infection. This PRISMA-compliant meta-analysis analysed the effectiveness of topical and/or intraventricular antibiotics in preventing shunt infections in patients undergoing shunt surgery.

Methods Four databases were searched from inception to 30th June 2021. Only original articles comparing the rate of shunt infection with and without antibiotics were included. Random-effects meta-analysis was used to compare the effect of the use of antibiotics in preventing infection and subgroup analysis for finding differences in various antibiotics.

Results The rate of shunt infection was 2.24% (53 out of 2362) in the topical antibiotic group in comparison to 5.24% (145 out of 2764) in the control group (p = 0.008). Subgroup analysis revealed that there is no significant difference between the antibiotics used.

Conclusions Our meta-analysis found that the risk of shunt infection is significantly reduced with the use of topical and intraventricular antibiotics without any serious adverse effect. No side effects of topical or intraventricular antibiotics were reported in the included studies. Further prospective studies are required to establish the safety and optimal dosage of topical antibiotics for them to be used routinely in neurosurgical practice. They can be used in patients at high risk of developing shunt infections till such studies are available.

The effectiveness of reducing endotracheal cuff pressure after retractor placement to decrease postoperative laryngeal dysfunction in anterior cervical surgery: a meta-analysis

J Neurosurg Spine 37:21–30, 2022

The authors sought to determine if a consensus could be reached regarding the effectiveness of endotracheal tube cuff pressure (ETTCP) reduction after retractor placement in reducing postoperative laryngeal dysfunction after anterior cervical fusion surgery.

METHODS A literature search of MEDLINE (PubMed), EMBASE, Cochrane Central, Google Scholar, and Scopus databases was performed. Quantitative analysis was performed on data from articles comparing groups of patients with either reduced or unadjusted ETTCP after retractor placement in the context of anterior cervical surgery. The incidence and severity of postoperative recurrent laryngeal nerve palsy (RLNP), dysphagia, and dysphonia were compared at several postsurgical time points, ranging from 24 hours to 3 months. Heterogeneity was assessed using the chi-square test, I 2 statistics, and inverted funnel plots. A random-effects model was used to provide a conservative estimate of the level of effect.

RESULTS Nine studies (7 randomized, 1 prospective, and 1 retrospective) were included in the analysis. A total of 1671 patients were included (1073 [64.2%] in the reduced ETTCP group and 598 [35.8%] in the unadjusted ETTCP group). In the reduced ETTCP group, the severity of dysphagia, measured by the Bazaz-Yoo system in 3 randomized studies at 24 hours and at 4–8 weeks, was significantly lower (24 hours [standardized mean difference: −1.83, p = 0.04] and 4–8 weeks [standardized mean difference: −0.40, p = 0.05]). At 24 hours, the odds of developing dysphonia were significantly lower (OR 0.51, p = 0.002). The odds of dysphagia (24 hours: OR 0.77, p = 0.24; 1 week: OR 0.70, p = 0.47; 12 weeks: OR 0.58, p = 0.20) were lower, although not significantly, in the reduced ETTCP group. The odds of a patient having RLNP were significantly lower at all time points (24 hours: OR 0.38, p = 0.01; 12 weeks: OR 0.26, p = 0.03) when 3 randomized and 2 observational studies were analyzed. A subgroup analysis using only randomized studies demonstrated a similar trend in odds of having RLNP, yet without statistical significance (24 hours: OR 0.79, p = 0.60). All other statistically significant findings persisted with removal of any observational data.

CONCLUSIONS Based on the current best available evidence, reduction of ETTCP after retractor placement in anterior cervical surgery may be a protective measure to decrease the severity of dysphagia and the odds of developing RLNP or dysphonia.

Insular epilepsy surgery: lessons learned from institutional review and patient-level meta-analysis

J Neurosurg 136:523–535, 2022

Insular lobe epilepsy is a challenging condition to diagnose and treat. Due to anatomical intricacy and proximity to eloquent brain regions, resection of epileptic foci in that region can be associated with significant postoperative morbidity. The aim of this study was to review available evidence on postoperative outcomes following insular epilepsy surgery.

METHODS A comprehensive literature search (PubMed/MEDLINE, Scopus, Cochrane) was conducted for studies investigating the postoperative outcomes for seizures originating in the insula. Seizure freedom at last follow-up (at least 12 months) comprised the primary endpoint. The authors also present their institutional experience with 8 patients (4 pediatric, 4 adult).

RESULTS A total of 19 studies with 204 cases (90 pediatric, 114 adult) were identified. The median age at surgery was 23 years, and 48% were males. The median epilepsy duration was 8 years, and 17% of patients had undergone prior epilepsy surgery. Epilepsy was lesional in 67%. The most common approach was transsylvian (60%). The most commonly resected area was the anterior insular region (n = 42, 21%), whereas radical insulectomy was performed in 13% of cases (n = 27). The most common pathology was cortical dysplasia (n = 68, 51%), followed by low-grade neoplasm (n = 16, 12%). In the literature, seizure freedom was noted in 60% of pediatric and 69% of adult patients at a median follow-up of 29 months (75% and 50%, respectively, in the current series). A neurological deficit occurred in 43% of cases (10% permanent), with extremity paresis comprising the most common deficit (n = 35, 21%), followed by facial paresis (n = 32, 19%). Language deficits were more common in left-sided approaches (24% vs 2%, p < 0.001). Univariate analysis for seizure freedom revealed a significantly higher proportion of patients with lesional epilepsy among those with at least 12 months of follow-up (77% vs 59%, p = 0.032).

CONCLUSIONS These findings may serve as a benchmark when tailoring decision-making for insular epilepsy, and may assist surgeons in their preoperative discussions with patients. Although seizure freedom rates are quite high with insular epilepsy treatment, the associated morbidity needs to be weighed against the potential for seizure freedom.