Olfactory groove meningioma

Olfactory groove meningioma



Olfactory groove meningiomas (OGMs) are arachnoid cell neoplasms of the frontoethmoidal suture and lamina cribrosa1) and may involve any part of the area from the crista galli to the planum sphenoidale 2) 3) 4).

The Meningiomas Arising from the Olfactory Groove and Their Removal by the Aid of Electro-surgery By Harvey Cushing · 1927


Cushing H, Eisenhardt L (1938) The olfactory meningiomas with primary anosmia. In: Cushing H, Eisenhardt L (eds) Meningiomas: their classification, regional behavior, life history, and surgical results. Charles C Thomas, Springfield, pp 250–282


Ojemann RG (1991) Olfactory groove meningiomas. In: Al-Mefty O (ed) Meningiomas. Raven Press, New York, pp 383–393


Al-Mefty O (1993) Tuberculum sellae and olfactory groove meningioma. In: Sekhar LN, Janecka IP (eds) Surgery of cranial base tumors. Raven Press, New York, pp 507–519


Surgery of Skull Base Meningiomas: With a Chapter Madjid Samii, ‎Mario Ammirati · 2012


Meningiomas of the Skull Base Treatment Nuances in Contemporary Neurosurgery 2018

A systematic review was performed to identify studies that compared outcomes following EEA and TCA for OGMs. Data extracted from each study included gross total resection (GTR), the incidence of cerebrospinal fluid (CSF) leaks, and post-operative complications including anosmia. The results of the search yielded 5 studies that met the criteria for inclusion and analysis. All studies compared TCA (n = 922) with EEA (n = 141) outcomes for OGMs. Overall, the rate of gross total resection (GTR) was lower among the endoscopic group (70.9%) relative to the transcranial group (91.5%). The rate of postoperative CSF leak was 6.3% vs. 25.5% for the transcranial and endoscopic groups, respectively. Post-operative anosmia was higher for patients undergoing EEA (95.9%) compared with patients in the transcranial group (37.4%). In this analysis, EEA was associated with a lower rate of GTR and higher incidences of CSF leaks and post-operative anosmia. However, with increasing surgeon familiarity with the endoscopic anatomy and technique for managing ASB pathologies, a nuanced approach may be used to minimize patient morbidity and widen the spectrum of skull base surgery 5).


Electronic databases were searched from inception until December 2019 for studies delineating TCAs for OGM patients. Patient demographics, pre-operative symptoms, surgical outcomes, and complications were evaluated and analyzed with a meta-analysis of proportions. Results: A total of 27 observational case series comparing 554 unilateral vs. 451 bilateral TCA patients were eligible for review. The weighted pooled incidence of gross total resection is 94.6% (95% CI, 90.7-97.5%; I 2 = 59.0%; p = 0.001) for unilateral and 90.9% (95% CI, 85.6-95.4%; I 2 = 58.1%; p = 0.003) for bilateral cohorts. Similarly, the incidence of OGM recurrence is 2.6% (95% CI, 0.4-6.0%; I 2 = 53.1%; p = 0.012) and 4.7% (95% CI, 1.4-9.2%; I 2 = 55.3%; p = 0.006), respectively. Differences in oncologic outcomes were not found to be statistically significant (p = 0.21 and 0.35, respectively). Statistically significant differences in complication rates in bilateral vs. unilateral TCA cohorts include meningitis (1.0 vs. 0.0%; p = 0.022) and mortality (3.2 vs. 0.2%; p = 0.007). Conclusions: While both cohorts have similar oncologic outcomes, bilateral TCA patients exhibit higher postoperative complication rates. This may be explained by underlying tumor characteristics necessitating more radical resection but may also indicate increased morbidity with bilateral approaches. However, evidence from more controlled, comparative studies is warranted to further support these findings 6).


A PubMed search of the recent literature (2011-2016) was performed to examine outcomes following EEA and TCA for OGM. The extent of resection, visual outcome, postoperative complications, and recurrence rates were analyzed using percentages and proportions, the Fischer exact test, and the Student’s t-test using GraphPad PRISM 7.0Aa (San Diego, CA) software.

Results: There were 444 patients in the TCA group with a mean diameter of 4.61 (±1.17) cm and 101 patients in the EEA group with a mean diameter of 3.55 (± 0.58) cm (p = 0.0589). GTR was achieved in 90.9% (404/444) in the TCA group and 70.2% (71/101) in the EEA group (p < 0.0001). Of the patients with preoperative visual disturbances, 80.7% (21/26) of patients in the EEA cohort had an improvement in vision compared to 12.83%(29/226) in the TCA group (p < 0.0001). Olfaction was lost in 61% of TCA and in 100% of EEA patients. CSF leaks and meningitis occurred in 25.7% and 4.95% of EEA patients and 6.3% and 1.12% of TCA patients, respectively (p < 0.0001; p = 0.023).

The updated literature review demonstrates that despite more experience with endoscopic resection and skull base reconstruction, the literature still supports TCA over EEA with respect to the extent of resection and complications. EEA may be an option in selected cases where visual improvement is the main goal of surgery and postoperative anosmia is acceptable to the patient or in medium-sized tumors with existing preoperative anosmia. Nevertheless, based on our results, it seems more prudent at this time to use TCA for the majority of OGMs 7).


1)

Guinto G. Olfactory Groove Meningiomaas. World Neurosurg. 2015 Jun;83(6):1046-7. doi: 10.1016/j.wneu.2014.12.044. Epub 2015 Jan 14. PMID: 25596435.
2)

Hentschel SJ, DeMonte F, Olfactory groove meningiomas. DeMonte F, McDermott MW, Al-Mefty O: Al-Mefty’s Meningiomas 2New York, Thieme, 2011. 196–205
3)

Nakamura M, Struck M, Roser F, Vorkapic P, Samii M: Olfactory groove meningiomas: clinical outcome and recurrence rates after tumor removal through the frontolateral and bifrontal approach. Neurosurgery 62:6 Suppl 31224–1232, 2008
4)

Pepper J, Hecht SL, Gebarski SS, Lin EM, Sullivan SE, Marentette LJ. Olfactory groove meningioma: discussion of clinical presentation and surgical outcomes following excision via the subcranial approach. Laryngoscope. 2011;121:2282–2289.
5)

Purohit A, Jha R, Khalafallah AM, Price C, Rowan NR, Mukherjee D. Endoscopic endonasal versus transcranial approach to resection of olfactory groove meningiomas: a systematic review. Neurosurg Rev. 2020 Dec;43(6):1465-1471. doi: 10.1007/s10143-019-01193-2. Epub 2019 Nov 10. PMID: 31709465.
6)

Feng AY, Wong S, Saluja S, Jin MC, Thai A, Pendharkar AV, Ho AL, Reddy P, Efron AD. Resection of Olfactory Groove Meningiomas Through Unilateral vs. Bilateral Approaches: A Systematic Review and Meta-Analysis. Front Oncol. 2020 Oct 22;10:560706. doi: 10.3389/fonc.2020.560706. PMID: 33194626; PMCID: PMC7642686.
7)

Shetty SR, Ruiz-Treviño AS, Omay SB, Almeida JP, Liang B, Chen YN, Singh H, Schwartz TH. Limitations of the endonasal endoscopic approach in treating olfactory groove meningiomas. A systematic review. Acta Neurochir (Wien). 2017 Oct;159(10):1875-1885. doi: 10.1007/s00701-017-3303-0. Epub 2017 Aug 22. PMID: 28831590.

Condoliase for lumbar disc herniation

Condoliase for lumbar disc herniation


Percutaneous chemonucleolysis with condoliase has been available for painful lumbar disc herniation since 2018 in Japan.


In the 1980s, chemonucleolysis with chymopapain, a protease, was widely used as the intermediate treatment between conservative therapy and surgical therapy in Western countries. However, since chymopapain was withdrawn from the market in 2002 for non-scientific commercial reasons, chemonucleolysis has not been a therapeutic option for LDH. Condoliase (chondroitin sulfate ABC endolyase), a glycosaminoglycan-degrading enzyme, was approved by the drug regulatory authority in Japan as a newer intradiscal therapy for LDH after clinical studies conducted in Japan demonstrated efficacy and safety for patients with LDH 1)


Condoliase as a first-line treatment option ahead of surgical treatment for LDH is superior, from a cost perspective to surgical treatment from the beginning. Condoliase is also a cost-effective alternative to non-surgery conservative treatment 2).

Patients between 20 and 70 years of age with unilateral leg pain, positive findings on the straight leg raise test, and LDH were recruited. All eligible patients were randomly assigned to receive condoliase (1.25, 2.5, or 5 U) or placebo. The primary end point was a change in the worst leg pain from preadministration (baseline) to week 13. The secondary end points were changes from baseline in the following items: worst back pain, Oswestry Disability Index (ODI), SF-36, and neurological examination. For pharmacokinetic and pharmacodynamic analyses, plasma condoliase concentrations and serum keratan sulfate concentrations were measured. The safety end points were adverse events (AEs) and radiographic and MRI parameters. Data on leg pain, back pain, abnormal neurological findings, and imaging parameters were collected until week 52. RESULTS A total of 194 patients received an injection of condoliase or placebo. The mean change in worst leg pain from baseline to week 13 was -31.7 mm (placebo), -46.7 mm (1.25 U), -41.1 mm (2.5 U), and -47.6 mm (5 U). The differences were significant at week 13 in the 1.25-U group (-14.9 mm; 95% CI -28.4 to -1.4 mm; p = 0.03) and 5-U group (-15.9 mm; 95% CI -29.0 to -2.7 mm; p = 0.01) compared with the placebo group. The dose-response improvement in the worst leg pain at week 13 was not significant (p = 0.14). The decrease in the worst leg pain in all 3 condoliase groups was observed from week 1 through week 52. Regarding the other end points, the worst back pain and results of the straight leg raise test, ODI, and SF-36 showed a tendency for sustained improvement in each of the condoliase groups until week 52. In all patients at all time points, plasma condoliase concentrations were below the detectable limit (< 100 μU/ml). Serum keratan sulfate concentrations significantly increased from baseline to 6 hours and 6 weeks after administration in all 3 condoliase groups. No patient died or developed anaphylaxis or neurological sequelae. Five serious AEs occurred in 5 patients (3 patients in the condoliase groups and 2 patients in the placebo group), resolved, and were considered unrelated to the investigational drug. Severe AEs occurred in 10 patients in the condoliase groups and resolved or improved. In the condoliase groups, back pain was the most frequent AE. Modic type 1 change and decrease in disc height were frequent imaging findings. Dose-response relationships were observed for the incidence of adverse drug reactions and decrease in disc height. CONCLUSIONS Condoliase significantly improved clinical symptoms in patients with LDH and was well tolerated. While all 3 doses had similar efficacy, the incidence of adverse drug reactions and decrease in disc height were dose dependent, thereby suggesting that 1.25 U would be the recommended clinical dose of condoliase. Clinical trial registration no.: NCT00634946 (clinicaltrials.gov) 3).

Ohtonari et al. investigated clinical and radiographic outcomes three months after the administration because secondary surgical removal is most required during this period for insufficient pain relief, and analyzed whether the differences in intradiscal injection areas affected the clinical outcomes. They retrospectively investigated 47 consecutive patients (males, 31; median age, 40 years) three months after the administration. Clinical outcomes were evaluated using the Japanese Orthopaedic Association Back Pain Questionnaire (JOABPEQ), a visual analog scale (VAS) score for low back pain, and VAS scores for pains and numbness in the lower limbs. Radiographic outcomes were analyzed in 41 patients, using parameters such as mid-sagittal disc height and maximal protrusion length of herniation on MRI preoperatively and at the final follow-up. The postoperative median evaluation period was 90 days. The effective rate of low back pain based on the pain-related disorders at baseline and the last follow-up in the JOABPEQ reached 79.5%. The postoperative proportion of VAS scores recovery ≥ 2 points and ≥ 50% for pains in the lower limbs were 80.9% and 66.0%, respectively, revealing satisfactory effectiveness. Preoperative median mid-sagittal disc height significantly reduced from 9.5 to 7.6 mm postoperatively. There were no significant differences in pain relief in the lower limbs by injection areas in the center and the dorsal 1/3rd near the herniation of the nucleus pulposus. Chemonucleolysis with condoliase revealed satisfactory short-term outcomes after the administration regardless of intradiscal injection areas 4).


101 patients who underwent chemonucleolysis with condoliase from January 2019 to December 2021. Patients were divided into good outcome (i.e., favorable outcome) and poor outcome (i.e., requiring additional surgical treatment) groups. Patient demographics and imaging findings were collected. Clinical outcomes were evaluated using the numerical rating scale and Japanese Orthopaedic Association scores at baseline and at 1- and 3-month follow-up. Pretreatment indicators for additional surgery were compared between the 2 groups. Results: There was a significant difference in baseline leg numbness between the good outcome and poor outcome groups (6.27 ± 1.90 vs. 4.42 ± 2.90, respectively; p = 0.033). Of the 101 included patients, 32 received a preoperative computed tomography scan. In those patients, the presence of calcification or ossification in disc hernia occurred more often in the poor outcome group (61.5% vs. 5.3%, respectively; p &lt; 0.001; odds ratio = 22.242; p = 0.014). Receiver-operating characteristics curve analysis for accompanying calcification or ossification showed an area under the curve of 0.858 (95% confidence interval, 0.715-1.000; p = 0.001). Conclusions: Calcified or ossified disc herniation may be useful predictors of unsuccessful treatment in patients with condoliase administration 5).


Sixty-seven patients (44 men, 23 women; mean age, 46.7 ± 18.0 years) were analyzed. Time-course changes in disc height, disc degeneration, and herniation size were assessed. For clinical outcomes assessment, visual analog scale (VAS) scores for leg and back pain and the Oswestry disability index (ODI) were obtained at baseline and the 3-month, 1-year, and 2-year follow-ups. We obtained a questionnaire from these patients at two years to assess satisfaction and recommendation. Condoliase therapy was considered to be effective in patients whose VAS score for leg pain improved by ≥ 50% at 2 years from baseline and who did not require surgery.

Results: Condoliase therapy was effective in 51 patients (76.1%). Eight patients (11.9%) required surgery due to ineffectiveness of the therapy. Condoliase therapy was ineffective in five out of six patients with a history of discectomy. The ODI and VAS scores for leg and back pain significantly improved from three months to two years. Of the patients, 80% satisfied with their outcomes, and 85% recommended this therapy. Progression of disc degeneration was observed in 57.1% of patients at three months; however, 30% recovered to baseline at two years. The mean disc height decreased at three months, but recovered slightly at one year and remained stable until two years. No recurrent disc herniation was observed.

Conclusions: Chemonucleolysis with condoliase was effective in 78% of patients with LDH for 2 years. Chemonucleolysis-induced disc degeneration was slightly recovered and maintained for two years post-injection. This treatment resulted in high patient satisfaction and recommendations 6).


137 LDH patients treated through condoliase at four Japanese institutions and assessed its effectiveness among different age categories on alleviation of visual analog scale (VAS) of leg pain, low back pain and numbness, as well as ODI and JOA scores. Moreover, we divided them into either a “group-A” category if a ≥50% improvement in baseline leg pain VAS was observed or “group-N” if VAS leg pain improved &lt;50%. Next, we assessed the differences in clinical and demographic distribution between group-A and group-N. Results: Fifty-five patients were classified as group-A (77.5%) and 16 patients were allocated to group-N (22.5%). A significant difference in Pfirrmann classification was found between both cohorts, with grade IV suggested to be most receptive. A posterior disc angle &gt; 5° was also found to approach statical significance. In all age groups, average VAS scores showed improvement. However, 75% of adolescent patients showed deterioration in Pfirrmann classification following treatment. Conclusions: Intradiscal condoliase injection is an effective treatment for LDH, even in patients with large vertebral translation and posterior disc angles, regardless of age. However, since condoliase imposes a risk of progressing disc degeneration, its indication for younger patients remains controversial 7).


Medical records and radiographic findings were reviewed retrospectively for 127 patients with LDH (88 male, 39 female, mean age: 46.6 ± 17.1 years, mean follow-up: 9.8 ± 7.8 months) who underwent chemonucleolysis with intradiscal condoliase injection at our center since September 2018. Condoliase (1.25 U/mL; 1 mL volume) was injected toward the middle of the affected intervertebral nucleus pulposus using a 21-gauge disc-puncture needle.

Results: Cases in which the Pfirrmann grade did and did not progress in the 3 months after the injection were included in groups P (progression, n = 49) and NP (non-progression, n = 78), respectively. Logistic regression analysis of progression of Pfirrmann grade post-injection showed significant associations with age <40 years (p = 0.013, odds ratio (OR): 3.69, 95% confidence interval (CI): 1.32-10.31), Pfirrmann Grade II or III at baseline (p = 0.021, OR: 3.51, 95% CI: 1.24-9.64), and a high-intensity MRI signal in the herniation (p = 0.047, OR: 2.97, 95% CI: 1.03-8.87). Patients in group P had significantly higher rates of disc height decrease ≥20%, reduced herniated disc size, and improved VAS for pain, but both groups had significant decreases in pain. No cases had an anaphylactic shock or neurologic sequelae.

Conclusions: These results show the safety and efficacy of chemonucleolysis with condoliase for treatment of painful LDH. Progression of Pfirrmann criteria on MRI at 3 months after injection was significantly associated with an improved clinical outcome 8).


Seventy patients (85.4%) were classified into the effective (E) group and 12 patients (14.6%) into the less-effective (L) group. Surgical treatment was required in four patients. No severe adverse complications were reported; 41.3% of the patients developed disc degeneration of Pfirrmann grade 1 or more at the injected disc level. Univariate analysis revealed that young age (p = 0.036), without history of epidural or nerve root block (p = 0.024), and injection into the central portion of the intervertebral disc (p = 0.014) were significantly associated with clinical effectiveness. A logistic regression analysis revealed that injection into the central portion of the intervertebral disc (p = 0.049; odds ratio, 4.913; 95% confidence interval, 1.006-26.204) was significantly associated with clinical effectiveness.

Conclusions: Chemonucleolysis with condoliase is a safe and effective treatment for painful LDH; 85.4% of the patients showed improvement after the treatment without severe adverse events. To obtain the best outcome, condoliase should be injected into the center of the intervertebral disc 9).


Forty-seven patients (20 women, 27 men; mean age 48 years) were included. The herniation level was L2/3 in one patient, L3/4 in two, L4/5 in 23, and L5/S1 in 21. Median symptom duration was 8 months. The mean VAS and ODI improved significantly from the baseline to 3-month follow-up (p < 0.01). Group E included 33 patients (70.2%) and group I included 14, three of whom had a history of discectomy. The rates of spondylolisthesis and posterior intervertebral angle ≥5° were significantly higher in group I than in group E. However, the rates of trans-ligamentous type and herniation with high signal intensity on T2-weighted images (highT2) were significantly higher in group E. Reduction of disc herniation was more frequently observed in group E.

Conclusions: Condoliase injection resulted in significantly improved symptoms in patients with LDH. Condoliase therapy was less effective for patients with a history of discectomy, spondylolisthesis, or those with a posterior intervertebral angle ≥5°, while trans-ligamentous type and high T2 herniation were associated with increased efficacy 10)


A total of 52 patients (mean age, 45.0 years) were enrolled and classified according to whether the injection was effective (E group, n=40, 76.9%) or less effective (L group, n=9, 17.3%). Three patients (5.8%) underwent herniotomy for residual pain within 6 months of the injection. There were no severe adverse events. Reduction of herniation was seen on MRI more often in the E group than in the L group. The effectiveness in patients with transligamentous LDH was similar to that in patients with subligamentous LDH. High-intensity signal change in the area of LDH on pretreatment T2-weighted MRI was a significant predictor of successful leg pain relief.

Conclusions: An intradiscal condoliase injection was a safe and effective treatment for painful radiculopathy caused by LDH. Leg pain was more likely to improve in patients with high-intensity signal change in the area of LDH before treatment 11).


In total, 84 patients were recruited (52 men, 32 women; mean age, 44.2 ± 17.1 [16-86 years]). The duration of illness was 6.7 ± 6.8 (1.5-30) months. All patient-based outcomes significantly improved at 4 weeks after the administration compared with pretreatment. The intervertebral disc height decreased significantly at four weeks after condoliase administration compared with that before administration. Progression of intervertebral disc degeneration occurred in 50% of the patients. Eleven patients underwent herniotomy due to poor treatment effects. Moreover, treatment in 77.4% of the patients was considered effective. A logistic regression analysis revealed that L5/S1 disk administration (p = 0.029; odds ratio, 5.94; 95% confidence interval, 1.20-29.45) were significantly associated with clinical effectiveness.

Conclusions: Condoliase disk administration improved pain and quality of life over time. Condoliase disk administration was more effective in L5/S1 intervertebral administration 12).


47 patients who received condoliase, 34 were enrolled in this study. The mean age of the patients was 33 years. The average duration since the onset of disease was 8.6 months. We evaluated patients’ low back and leg pain using a numerical rating scale (NRS) score at two time points (before therapy and 3 months after therapy). We divided the patients into two groups (good group (G): NRS score improvement ≥ 50%, poor group (P): NRS score improvement < 50%). The parameters evaluated were age, disease duration, body mass index (BMI), and positive or negative straight leg raising test results. In addition, the loss of disc height and preoperative radiological findings were evaluated. Results: In terms of low back and leg pain, the G group included 9/34 (26.5%) and 21/34 (61.8%) patients, respectively. Patients’ age (low back pain G/P, 21/36.5 years) was significantly lower in the G group for low back pain (p = 0.001). High-intensity change in the protruded nucleus pulposus (NP) and spinal canal occupancy by the NP ≥ 40% were significantly high in those with leg pain in the G groups (14/21, p = 0.04; and 13/21, p = 0.03, respectively). Conclusions: The efficacy of improvement in leg pain was significantly correlated with high-intensity change and size of the protruded NP. Condoliase was not significantly effective for low back pain but could have an effect on younger patients 13).


42 patients with LDH who underwent intradiscal condoliase injection. Patients with and without a ≥50% improvement from baseline of leg pain at 3 months after injection were defined as responders and non-responders, respectively. Clinical features and radiological findings were compared between these groups.

Results: Of the 42 patients, 32 (76.2%) were responders and 10 (23.8%) were non-responders. Of 8 patients with a history of discectomy at the same level as LDH, 6 (75.0%) were responders. Non-responders had a significantly longer time from onset to treatment, smaller herniated volume before treatment, lower percentage reduction of herniated mass, and less intervertebral disc degeneration before treatment. There were no significant differences in LDH types (subligamentous extrusion or transligamentous extrusion types), high-intensity area within the herniation, changes in disc height, and region of condoliase injection between the two groups.

Conclusions: Intradiscal condoliase injection had a good short-term therapeutic effect in patients with LDH, including in transligamentous extrusion-type and revision cases as well as subligamentous extrusion-type cases. Administration of intradiscal condoliase injection may be most effective in patients with a larger herniated mass volume before treatment, and least effective in cases with a longer time and less intervertebral disc degeneration before treatment 14).


A total of 82 and 81 patients received an injection of condoliase and placebo, respectively. The average changes in worst leg pain from baseline to week 13 (primary endpoint) were -49.5 mm in the condoliase group and -34.3 mm in the placebo group, and the difference of -15.2 mm was significant (95% confidence interval, -24.2 to -6.2; P = 0.001). Significant improvements were observed in the condoliase groups, compared with the placebo group, in most secondary endpoints at 1 year after administration. In the condoliase group, back pain, Modic type 1 change, and decrease in disc height were frequently reported, without any clinically relevant consequences.

Conclusion: Condoliase significantly improved symptoms in patients with LDH and was well tolerated. Condoliase is a novel and potent chemonucleolytic drug for the treatment of LDH 15).

It has been available for painful lumbar disc herniation since 2018 in Japan.

A 25-year-old man with a history of LDH in L4/5, who underwent transforaminal full endoscopic lumbar discectomy when he was 17 years old, complained of severe pain radiating to his left leg for 1 month. The straight leg-raising test was limited to 25° on the left side. Lumbar T2-weighted magnetic resonance imaging (MRI) showed intracanal, left-sided transligamentous disc herniation at L4/5 with high-signal intensity. Because the conservative treatment with oral analgesics and selective left L5 nerve root block failed, the patient requested intradiscal condoliase injection instead of revision surgery. There were no adverse events reported after the condoliase treatment, and the pain radiating to the left leg improved within 2 weeks. A lumbar MRI performed 2 months after treatment revealed that the disc herniation had significantly decreased in size. The straight leg-raising test examined 3 months after treatment was negative. In this case, the disc herniation was of the transligamentous type and showed a high-signal intensity on T2-weighted MRI which could be suitably treated by condoliase injection therapy. This case report is the first to suggest that intradiscal condoliase injection could be a useful and novel conservative treatment option to treat postoperative rec-LDH 16).


1)

Matsuyama Y, Chiba K. Condoliase for treatment of lumbar disc herniation. Drugs Today (Barc). 2019 Jan;55(1):17-23. doi: 10.1358/dot.2019.55.1.2899445. PMID: 30740609.
2)

Takaki S, Miyama H, Iwasaki M. Cost-effectiveness analysis of intradiscal condoliase injection vs. surgical or conservative treatment for lumbar disc herniation. J Med Econ. 2023 Jan-Dec;26(1):233-242. doi: 10.1080/13696998.2023.2173465. PMID: 36794375.
3)

Matsuyama Y, Chiba K, Iwata H, Seo T, Toyama Y. A multicenter, randomized, double-blind, dose-finding study of condoliase in patients with lumbar disc herniation. J Neurosurg Spine. 2018 May;28(5):499-511. doi: 10.3171/2017.7.SPINE161327. Epub 2018 Feb 9. PMID: 29424676.
4)

Ohtonari T, Torii R, Noguchi S, Kitagawa T, Nishihara N. Short-term clinical and radiographic outcomes of chemonucleolysis with condoliase for painful lumbar disc herniation and analysis regarding intradiscal injection area. Neurosurg Rev. 2023 Feb 23;46(1):59. doi: 10.1007/s10143-023-01966-w. PMID: 36813932.
5)

Takeuchi S, Hanakita J, Takahashi T, Inoue T, Minami M, Suda I, Nakamura S, Kanematsu R. Predictive Factors for Poor Outcome following Chemonucleolysis with Condoliase in Lumbar Disc Herniation. Medicina (Kaunas). 2022 Dec 18;58(12):1868. doi: 10.3390/medicina58121868. PMID: 36557070; PMCID: PMC9781337.
6)

Banno T, Hasegawa T, Yamato Y, Yoshida G, Arima H, Oe S, Ide K, Yamada T, Kurosu K, Nakai K, Matsuyama Y. Condoliase therapy for lumbar disc herniation -2 year clinical outcome. J Orthop Sci. 2022 Nov 21:S0949-2658(22)00317-7. doi: 10.1016/j.jos.2022.11.005. Epub ahead of print. PMID: 36424250.
7)

Oshita Y, Matsuyama D, Sakai D, Schol J, Shirasawa E, Emori H, Segami K, Takahashi S, Yagura K, Miyagi M, Saito W, Imura T, Nakazawa T, Inoue G, Hiyama A, Katoh H, Akazawa T, Kanzaki K, Sato M, Takaso M, Watanabe M. Multicenter Retrospective Analysis of Intradiscal Condoliase Injection Therapy for Lumbar Disc Herniation. Medicina (Kaunas). 2022 Sep 15;58(9):1284. doi: 10.3390/medicina58091284. PMID: 36143959; PMCID: PMC9501482.
8)

Kobayashi K, Sato K, Ando T. Factors associated with disc degeneration based on Pfirrmann criteria after condoliase treatment for lumbar disc herniation. J Orthop Sci. 2022 Aug 24:S0949-2658(22)00230-5. doi: 10.1016/j.jos.2022.08.001. Epub ahead of print. PMID: 36030156.
9)

Okada E, Suzuki S, Nori S, Tsuji O, Nagoshi N, Yagi M, Fujita N, Nakamura M, Matsumoto M, Watanabe K. The effectiveness of chemonucleolysis with condoliase for treatment of painful lumbar disc herniation. J Orthop Sci. 2021 Jul;26(4):548-554. doi: 10.1016/j.jos.2020.06.004. Epub 2020 Jul 23. PMID: 32713796.
10)

Banno T, Hasegawa T, Yamato Y, Yoshida G, Yasuda T, Arima H, Oe S, Ushirozako H, Yamada T, Ide K, Watanabe Y, Matsuyama Y. Clinical outcome of condoliase injection treatment for lumbar disc herniation: Indications for condoliase therapy. J Orthop Sci. 2021 Jan;26(1):79-85. doi: 10.1016/j.jos.2020.02.002. Epub 2020 Feb 25. PMID: 32111547.
11)

Hirai T, Takahashi T, Tanaka T, Motoyoshi T, Matsukura Y, Yuasa M, Inose H, Yoshii T, Okawa A. Intradiscal Injection with Condoliase (Chondroitin Sulfate ABC Endolyase) for Painful Radiculopathy Caused by Lumbar Disc Herniation. Spine Surg Relat Res. 2021 Oct 11;6(3):252-260. doi: 10.22603/ssrr.2021-0151. PMID: 35800623; PMCID: PMC9200423.
12)

Inoue M, Sainoh T, Kojima A, Yamagata M, Morinaga T, Mannoji C, Ataka H, Yamashita M, Takahashi H, Saito J, Fujiyoshi T, Ishikawa T, Eguchi Y, Kato K, Orita S, Inage K, Shiga Y, Norimoto M, Umimura T, Shiko Y, Kawasaki Y, Aoki Y, Ohtori S. Efficacy and Safety of Condoliase Disc Administration as a New Treatment for Lumbar Disc Herniation. Spine Surg Relat Res. 2021 Jun 11;6(1):31-37. doi: 10.22603/ssrr.2021-0035. PMID: 35224244; PMCID: PMC8842352.
13)

Ishibashi K, Fujita M, Takano Y, Iwai H, Inanami H, Koga H. Chemonucleolysis with Chondroitin Sulfate ABC Endolyase for Treating Lumbar Disc Herniation: Exploration of Prognostic Factors for Good or Poor Clinical Outcomes. Medicina (Kaunas). 2020 Nov 19;56(11):627. doi: 10.3390/medicina56110627. PMID: 33228119; PMCID: PMC7699387.
14)

Nakajima H, Kubota A, Maezawa Y, Watanabe S, Honjoh K, Ohmori H, Matsumine A. Short-Term Outcome and Predictors of Therapeutic Effects of Intradiscal Condoliase Injection for Patients with Lumbar Disc Herniation. Spine Surg Relat Res. 2020 Nov 20;5(4):264-271. doi: 10.22603/ssrr.2020-0126. PMID: 34435150; PMCID: PMC8356240.
15)

Chiba K, Matsuyama Y, Seo T, Toyama Y. Condoliase for the Treatment of Lumbar Disc Herniation: A Randomized Controlled Trial. Spine (Phila Pa 1976). 2018 Aug 1;43(15):E869-E876. doi: 10.1097/BRS.0000000000002528. PMID: 29257028.
16)

Funayama T, Setojima Y, Shibao Y, Noguchi H, Miura K, Eto F, Sato K, Kono M, Asada T, Takahashi H, Tatsumura M, Koda M, Yamazaki M. A Case of Postoperative Recurrent Lumbar Disc Herniation Conservatively Treated with Novel Intradiscal Condoliase Injection. Case Rep Orthop. 2022 Feb 15;2022:3656753. doi: 10.1155/2022/3656753. PMID: 35211348; PMCID: PMC8863464.

Central nervous system tumor guidelines

Central nervous system tumor guidelines

The NCCN Guidelines for Central nervous system tumor focus on the management of the following adult CNS cancers: glioma (WHO grade 1, WHO grade 2-3 Oligodendroglioma IDH-mutant and 1p/19q-codeleted, WHO grade 2-4 Astrocytoma IDH-mutants, WHO grade 4 glioblastoma), intracranial and spinal ependymomas, medulloblastoma, limited and extensive brain metastasesleptomeningeal metastases, non-AIDS-related Primary central nervous system lymphomas, metastatic spine tumors, meningiomas, and primary spinal cord tumors. The information contained in the algorithms and principles of management sections in the NCCN Guidelines for CNS Cancers is designed to help clinicians navigate through the complex management of patients with CNS tumors. Several important principles guide surgical management and treatment with radiotherapy and systemic therapy for adults with brain tumors. The NCCN CNS Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding molecular profiling of glioma1)

Evidence-based, clinical practice guidelines in the management of central nervous system tumors (CNS) continue to be developed and updated through the work of the Joint Section on Tumors of the Congress of Neurological Surgeons (CNS) and the American Association of Neurological Surgeons (AANS).

The guidelines are created using the most current and clinically relevant evidence using systematic methodologies, which classify available data and provide recommendations for clinical practice.

This update summarizes the Tumor Section Guidelines developed over the last five years for non-functioning pituitary adenomas, low-grade gliomas, vestibular schwannomas, and metastatic brain tumors 2).


1)

Horbinski C, Nabors LB, Portnow J, Baehring J, Bhatia A, Bloch O, Brem S, Butowski N, Cannon DM, Chao S, Chheda MG, Fabiano AJ, Forsyth P, Gigilio P, Hattangadi-Gluth J, Holdhoff M, Junck L, Kaley T, Merrell R, Mrugala MM, Nagpal S, Nedzi LA, Nevel K, Nghiemphu PL, Parney I, Patel TR, Peters K, Puduvalli VK, Rockhill J, Rusthoven C, Shonka N, Swinnen LJ, Weiss S, Wen PY, Willmarth NE, Bergman MA, Darlow S. NCCN Guidelines® Insights: Central Nervous System Cancers, Version 2.2022. J Natl Compr Canc Netw. 2023 Jan;21(1):12-20. doi: 10.6004/jnccn.2023.0002. PMID: 36634606.
2)

Redjal N, Venteicher AS, Dang D, Sloan A, Kessler RA, Baron RR, Hadjipanayis CG, Chen CC, Ziu M, Olson JJ, Nahed BV. Guidelines in the management of CNS tumors. J Neurooncol. 2021 Feb;151(3):345-359. doi: 10.1007/s11060-020-03530-8. Epub 2021 Feb 21. PMID: 33611702.

Cerebellar mutism

Cerebellar mutism

Incidence of cerebellar mutism: 11–29% of children following surgery for cerebellar tumor2) including cerebellar medulloblastoma (53%), posterior fossa ependymoma (33%) & cerebellar pilocytic astrocytoma (11%) 3).

It has also been reported in both children and adults following several other cerebellar insults, including vascular events, infections, and trauma 4).

The uncertain etiology of PFS, myriad of cited risk factors and therapeutic challenges make this phenomenon an elusive entity.

Cerebellar mutism is a rare occurrence following paediatric trauma 5) 6) 7) 8). , this phenomenon has rarely been reported following other insults, such as trauma, and its pathophysiology remains poorly understood.

A seven-year-old child who presented to the casualty department of Sultan Qaboos University Hospital in Muscat, Oman, in May 2013 with a traumatic right cerebellar contusion. The child presented with clinical features of cerebellar mutism but underwent a rapid and spontaneous recovery 9).

The pathogenic mechanism is likely due to the damage occurring to the proximal efferent cerebellar pathway, including the dentate nucleus, the superior cerebellar peduncle, and its decussation in the mesencephalic tegmentum 10).

Superior and inferior cerebellar peduncles and the superior part of the cerebellum were related to CMS, especially the right side 11).

This syndrome involves a variety of signs and symptoms including cerebellar mutism or speech disturbances, dysphagia, decreased motor movement, cranial nerve palsy and, emotional lability. These signs and symptoms develop from an average range of 24 to 107 hours after surgery and may take weeks to months to resolve.

Multi-inflow time arterial spin-labeling shows promise as a noninvasive tool to evaluate cerebral perfusion in the setting of pediatric obstructive hydrocephalus and demonstrates increased CBF following the resolution of cerebellar mutism syndrome 12).

The importance of olivary hypertrophic degeneration as a differential diagnosis in cerebellar mutism syndrome 13).

Early recognition of this syndrome could facilitate preventive and restorative patient care, prevent subsequent complications, decrease length of hospital stays, and promote patient and family understanding of and coping with the syndrome 14).

20 cases of PFS (8%), 12 males and 8 females. Age ranged from 1.5 to 13 years (mean = 6.5). Of the 20, 16 were medulloblastoma, 3 ependymoma and 1 astrocytoma. There was a 21 % incidence (16/76) of PFS in medulloblastoma of the posterior fossa. The incidence for ependymoma was 13% (3/24) and 1% (1/102) for astrocytoma. All 20 cases (100%) had brainstem involvement by the tumor. The most frequent postoperative findings included mutism, ataxia, 6th and 7th nerve palsies and hemiparesis. Mutism had a latency range of 1-7 days (mean = 1.7) and a duration of 6-365 days (mean = 69.2, median = 35). Although mutism resolved in all cases, the remaining neurologic complications which characterized our findings of PFS were rarely reversible. We describe potential risk factors for developing PFS after surgery with hopes of making neurosurgeons more aware of potential problems following the removal of lesions in this area. Early recognition of PFS would further promote patient and family understanding and coping with this síndrome 15)


19 children diagnosed with posterior fossa syndrome 16)


1)

Rekate HL, Grubb RL, Aram DM, Hahn JF, Ratcheson RA. Muteness of cerebellar origin. Arch Neurol. 1985;42:697–8. doi: 10.1001/archneur.1985.04060070091023.
2)

Gudrunardottir T, Sehested A, Juhler M, et al. Cerebellar mutism: review of the literature. Childs Nerv Syst. 2011; 27:355–363
3)

Catsman-Berrevoets C E, Van Dongen HR, Mulder PG, et al. Tumour type and size are high risk factors for the syndrome of “cerebellar” mutism and subsequent dysarthria. J Neurol Neurosurg Psychiatry. 1999; 67:755–757
4)

Gudrunardottir T, Sehested A, Juhler M, Schmiegelow K. Cerebellar mutism: Review of the literature. Childs Nerv Syst. 2011;27:355–63. doi: 10.1007/s00381-010-1328-2.
5)

Erşahin Y, Mutluer S, Saydam S, Barçin E. Cerebellar mutism: Report of two unusual cases and review of the literature. Clin Neurol Neurosurg. 1997;99:130–4. doi: 10.1016/S0303-8467(97)80010-8.
6)

Fujisawa H, Yonaha H, Okumoto K, Uehara H, le T, Nagata Y, et al. Mutism after evacuation of acute subdural hematoma of the posterior fossa. Childs Nerv Syst. 2005;21:234–6. doi: 10.1007/s00381-004-0999-y.
7)

Koh S, Turkel SB, Baram TZ. Cerebellar mutism in children: Report of six cases and potential mechanisms. Pediatr Neurol. 1997;16:218–19. doi: 10.1016/S0887-8994(97)00018-0.
8)

Yokota H, Nakazawa S, Kobayashi S, Taniguchi Y, Yukihide T. [Clinical study of two cases of traumatic cerebellar injury] No Shinkei Geka. 1990;18:67–70.
9)

Kariyattil R, Rahim MI, Muthukuttiparambil U. Cerebellar mutism following closed head injury in a child. Sultan Qaboos Univ Med J. 2015 Feb;15(1):e133-5. Epub 2015 Jan 21. PubMed PMID: 25685374; PubMed Central PMCID: PMC4318595.
10)

Fabozzi F, Margoni S, Andreozzi B, Musci MS, Del Baldo G, Boccuto L, Mastronuzzi A, Carai A. Cerebellar mutism syndrome: From pathophysiology to rehabilitation. Front Cell Dev Biol. 2022 Dec 2;10:1082947. doi: 10.3389/fcell.2022.1082947. PMID: 36531947; PMCID: PMC9755514.
11)

Yang W, Li Y, Ying Z, Cai Y, Peng X, Sun H, Chen J, Zhu K, Hu G, Peng Y, Ge M. A presurgical voxel-wise predictive model for cerebellar mutism syndrome in children with posterior fossa tumors. Neuroimage Clin. 2022 Dec 13;37:103291. doi: 10.1016/j.nicl.2022.103291. Epub ahead of print. PMID: 36527996; PMCID: PMC9791171.
12)

Toescu SM, Hales PW, Cooper J, Dyson EW, Mankad K, Clayden JD, Aquilina K, Clark CA. Arterial Spin-Labeling Perfusion Metrics in Pediatric Posterior Fossa Tumor Surgery. AJNR Am J Neuroradiol. 2022 Oct;43(10):1508-1515. doi: 10.3174/ajnr.A7637. Epub 2022 Sep 22. PMID: 36137658; PMCID: PMC9575521.
13)

Ballestero M, de Oliveira RS. The importance of olivary hypertrophic degeneration as a differential diagnosis in cerebellar mutism syndrome. Childs Nerv Syst. 2022 Dec 21. doi: 10.1007/s00381-022-05815-x. Epub ahead of print. PMID: 36542117.
14) , 16)

Kirk EA, Howard VC, Scott CA. Description of posterior fossa syndrome in children after posterior fossa brain tumor surgery. J Pediatr Oncol Nurs. 1995 Oct;12(4):181-7. PubMed PMID: 7495523.
15)

Doxey D, Bruce D, Sklar F, Swift D, Shapiro K. Posterior fossa syndrome: identifiable risk factors and irreversible complications. Pediatr Neurosurg. 1999 Sep;31(3):131-6. PubMed PMID: 10708354.

Tranexamic acid for intracranial meningioma

Tranexamic acid for intracranial meningioma

Based upon Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), Wijaya et al. from the Universitas Pelita Harapan, Tangerang, BantenIndonesia, Cedars-Sinai Medical Center, Los Angeles, CES University, El Poblado, Medellín, Antioquia, Colombia. collected fully published English literature on the administration of tranexamic acid for patients undergoing intracranial meningioma surgery using the keywords [“tranexamic acid” and “meningioma”] and its synonyms from Cochrane Central Register of Controlled Trials Database, the WHO International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, and PubMed. The primary outcome of the current study was total blood loss. The secondary outcomes include individuals requiring blood transfusionanesthesia duration, surgical duration, and complication rate. Each included study’s quality was assessed using the JADAD scale.

For qualitative and quantitative data synthesis, they included five RCTs (n = 321) with a mean age was 47.5 ± 11.9 years for the intervention group and 47.2 ± 11.9 years for the control group. The meta-analysis showed that the administration of TXA is associated with decreased total blood loss of standardized mean difference (SMD) of -1.40 (95% CI [-2.49, -0.31]), anesthetic time SMD -0.36 (95% CI [-0.63, -0.09]), and blood transfusion requirements RR 0.58 (95% CI [0.34, 0.99]).

The current study showed that TXA was associated with reduced intraoperative blood loss and intraoperative and postoperative blood transfusion. However, the studies are small. More RCT studies with a greater sample size are favorable 1).

Patients with supratentorial meningiomas and deemed suitable for surgical resection will be recruited in the trial. Patients will be randomized to receive either a single administration of 20 mg/kg TXA or a placebo of the same volume with a 1:1 allocation ratio after anesthesia induction. The primary endpoint is the cumulative incidence of early postoperative seizures within 7 days after craniotomy. Secondary outcomes include the incidence of non-seizure complications, changes in hemoglobin level from baseline, intraoperative blood loss, erythrocyte transfusion volume, Karnofsky Performance Status, all-cause mortality, length of stay, and total hospitalization cost.

Ethics and dissemination: This trial is registered at ClinicalTrial.gov and approved by the Chinese Ethics Committee of Registering Clinical Trials (ChiECRCT20200224). The findings will be disseminated in peer-reviewed journals and presented at national or international conferences relevant to the subject fields.

Trial registration number: NCT04595786 2).


conducted a prospective, randomized double-blind clinical study. The patient scheduled to undergo excision of intracranial meningioma were randomly assigned to receive intraoperatively either intravenous TXA or placebo. Patients in the TXA group received an intravenous bolus of 20 mg/kg over 20 min followed by an infusion of 1 mg/kg/h up to surgical wound closure. Efficacy was evaluated based on total blood loss and transfusion requirements. Postoperatively, thrombotic complications, convulsive seizure, and hematoma formation were noted.

Ninety-one patients were enrolled and randomized: 45 received TXA (TXA group) and 46 received placebo (group placebo). Total blood loss was significantly decreased in the TXA group compared to the placebo (283 ml vs. 576 ml; P < 0.001). Transfusion requirements were comparable in the two groups (P = 0.95). The incidence of thrombotic complications, convulsive seizure, and hematoma formation were similar in the two groups.

TXA significantly reduces intraoperative blood loss but did not significantly reduce transfusion requirements in adults undergoing resection of intracranial meningioma 3).

Thirty patients aged 18-65 years undergoing elective meningioma resection surgery were given either tranexamic acid or placebo (0.9% saline), tranexamic acid at a loading dose of 20 mg/kg, and infusion of 1 mg/kg/h during surgery. The intraoperative blood loss, coagulation profile, and the surgical field using the Likert scale were assessed.

The patients in the tranexamic group had significantly decreased intraoperative blood loss compared to the placebo group (616.42 ± 393.42 ml vs. 1150.02 ± 416.1 ml) (P = 0.02). The quality of the surgical field was better in the tranexamic group (median score 4 vs. 2 on Likert Scale) (P < 0.001). Patients in the tranexamic group had an improved coagulation profile and decreased blood transfusion requirement (p=0.016). The blood collected in the closed suction drain in 24 h postsurgery was less in the tranexamic acid group compared to the placebo group (84.7 ± 50.4 ml vs. 127.6 ± 62.2 ml) (P = 0.047).

Tranexamic acid bolus followed by infusion reduces perioperative blood loss by 46.43% and blood transfusion requirement with improved surgical field and coagulation profile in patients undergoing intracranial meningioma resection surgery 4).


In the Department of Neurosurgery, All India Institute of Medical Sciences (AIIMS), New Delhi, India, Sixty adults undergoing elective craniotomy for meningioma excision were randomized to receive either tranexamic acid or placebo, initiated prior to skin incision. Patients in the tranexamic acid group received an intravenous bolus of 20mg/kg over 20min followed by an infusion of 1mg/kg/h till the conclusion of surgery. Intraoperative blood loss, transfusion requirements, and estimating surgical hemostasis using a 5-grade scale were noted. Postoperatively, the extent of tumor excision on CT scan and complications were observed. Demographics, tumor characteristics, amount of fluid infusion, and duration of surgery and anesthesia were comparable between the two groups. The amount of blood loss was significantly less in the tranexamic acid group compared to the placebo (830mlvs 1124ml; p=0.03). The transfusion requirement was less in the tranexamic acid group (p>0.05). The patients in the tranexamic acid group fared better on a 5-grade surgical hemostasis scale with more patients showing good hemostasis (p=0.007). There were no significant differences between the groups regarding the extent of tumor removal, perioperative complications, hospital stay, or neurologic outcome. To conclude, the administration of tranexamic acid significantly reduced blood loss in patients undergoing excision of meningioma. Fewer patients in the tranexamic acid group received blood transfusions. Surgical field hemostasis was better achieved in patients who received tranexamic acid 5).

A man in his 40s with a history of coronary artery disease previously treated with a drug-eluting stent presented for elective craniotomy and resection of an asymptomatic but enlarging meningioma. During his craniotomy, he received desmopressin and tranexamic acid for surgical bleeding. Postoperatively, the patient developed chest pain and was found to have an ST-elevation myocardial infarction (MI). Because of the patient’s recent neurosurgery, standard post-MI care was contraindicated and he was managed symptomatically in the intensive care unit. The echocardiogram on a postoperative day 1 demonstrated no regional wall motion abnormalities and an ejection fraction of 60%. His presentation was consistent with the thrombosis of his diagonal stent. He was transferred out of the intensive care unit on postoperative day 1 and discharged home on postoperative day 3 6).


Raghavendra et al. report the intraoperative use of tranexamic acid to secure complete hemostasis as a rescue measure in intracranial meningioma resection in uncontrollable bleeding 7).


Three of 13 patients with intracranial meningiomas showed the pre-and postoperative elevation of tissue-type plasminogen activator (t-PA) related fibrinolytic activity in euglobulin fractions (EFA). During the operation, two of these three patients showed a significant elevation of the level of fibrinogen degradation products and oozing in the operating field. However, oozing was not observed in the third patient who had been given tranexamic acid preoperatively. Fibrin autography revealed that a broad lytic band of mol wt 50-60 kDa, probably free t-PA, appeared in the plasma obtained from two of the three patients after the operation when EFA elevated significantly. In all patients studied, the t-PA antigen levels were normal preoperatively but increased both during and after the operation, and correlated mainly with the intensities of a lytic band of mol wt 110 kDa, probably t-PA complexed with its major inhibitor (PAI-1). These results suggest that excessive fibrinolysis can induce local hemorrhagic diathesis during operation and may be related to t-PA function in plasma 8).


1)

Wijaya JH, July J, Quintero-Consuegra M, Chadid DP. A systematic review and meta-analysis of the effects of tranexamic acid in surgical procedure for intracranial meningioma. J Neurooncol. 2023 Jan 12. doi: 10.1007/s11060-023-04237-2. Epub ahead of print. PMID: 36633801.
2)

Li S, Yan X, Li R, Zhang X, Ma T, Zeng M, Dong J, Wang J, Liu X, Peng Y. Safety of intravenous tranexamic acid in patients undergoing supratentorial meningiomas resection: protocol for a randomized, parallel-group, placebo control, non-inferiority trial. BMJ Open. 2022 Feb 2;12(2):e052095. doi: 10.1136/bmjopen-2021-052095. PMID: 35110315; PMCID: PMC8811564.
3)

Rebai L, Mahfoudhi N, Fitouhi N, Daghmouri MA, Bahri K. Intraoperative tranexamic acid use in patients undergoing excision of intracranial meningioma: Randomized, placebo-controlled trial. Surg Neurol Int. 2021 Jun 14;12:289. doi: 10.25259/SNI_177_2021. PMID: 34221620; PMCID: PMC8247750.
4)

Ravi GK, Panda N, Ahluwalia J, Chauhan R, Singla N, Mahajan S. Effect of tranexamic acid on blood loss, coagulation profile, and quality of the surgical field in intracranial meningioma resection: A prospective randomized, double-blind, placebo-controlled study. Surg Neurol Int. 2021 Jun 7;12:272. doi: 10.25259/SNI_296_2021. PMID: 34221603; PMCID: PMC8247710.
5)

Hooda B, Chouhan RS, Rath GP, Bithal PK, Suri A, Lamsal R. Effect of tranexamic acid on intraoperative blood loss and transfusion requirements in patients undergoing excision of intracranial meningioma. J Clin Neurosci. 2017 Mar 7. pii: S0967-5868(16)31491-6. doi: 10.1016/j.jocn.2017.02.053. [Epub ahead of print] PubMed PMID: 28283245.
6)

Westfall KM, Ramcharan RN, Anderson HL 3rd. Myocardial infarction after craniotomy for asymptomatic meningioma. BMJ Case Rep. 2022 Dec 29;15(12):e252256. doi: 10.1136/bcr-2022-252256. PMID: 36581354; PMCID: PMC9806024.
7)

Raghavendra H, Varsha KS, Reddy MA, Kumar SS, Sunanda G, Nagarjuna T, Latha S. Rescue Measure in Giant Intracranial Meningioma Resection by Tranexamic Acid. J Neurosci Rural Pract. 2017 Aug;8(Suppl 1):S127-S129. doi: 10.4103/jnrp.jnrp_198_17. PMID: 28936089; PMCID: PMC5602238.
8)

Tsuda H, Oka K, Noutsuka Y, Sueishi K. Tissue-type plasminogen activator in patients with intracranial meningiomas. Thromb Haemost. 1988 Dec 22;60(3):508-13. PMID: 3149049.

Cervical Sympathetic Nerve Block for cerebral vasospasm

Cervical Sympathetic Nerve Block for cerebral vasospasm

Sympathetic perivascular nerve fibers originate from the superior cervical ganglion (SCG) to innervate the cerebral vasculature, with activation resulting in vasoconstriction. Sympathetic pathways are thought to be a significant contributor to cerebral vasospasm 1).


A simple treatment such as a cervical sympathetic nerve block may be an effective therapy but is not routinely performed as cerebral vasospasm treatment/DCI. cervical sympathetic nerve block consists of injecting local anesthetic at the level of the cervical sympathetic trunk, which temporarily blocks the innervation of the cerebral arteries to cause arterial vasodilatation. cervical sympathetic nerve block is a local, minimally invasive, low cost and safe technique that can be performed at the bedside and may offer significant advantages as a complementary treatment in combination with more conventional neurointerventional surgery interventions. Bombardieri et al. reviewed the literature that describes cervical sympathetic nerve block for vasospasm/DCI prevention or treatment in humans after aSAH. The studies outlined in this review show promising results for a cervical sympathetic nerve block as a treatment for vasospasm/DCI. Further research is required to standardize the technique, explore how to integrate a cervical sympathetic nerve block with conventional neurointerventional surgery treatments of vasospasm and DCI, and study its long-term effect on neurological outcomes 2).


SCG was surgically identified in 15 swine and were electrically stimulated to achieve sympathetic activation. CT perfusion scans were performed to assess for changes in cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time-to-maximum (TMax). Syngo. via software was used to determine regions of interest and quantify perfusion measures.

Results: SCG stimulation resulted in 20-30% reduction in mean ipsilateral CBF compared to its contralateral unaffected side (p < 0.001). Similar results of hypoperfusion were seen with CBV, MTT and TMax with SCG stimulation. Prior injection of lidocaine to SCG inhibited the effects of SCG stimulation and restored perfusion comparable to baseline (p > 0.05).

Conclusion: In swine, SCG stimulation resulted in significant cerebral perfusion deficit, and this was inhibited by prior local anesthetic injection into the SCG. Inhibiting sympathetic activation by targeting the SCG may be an effective treatment for sympathetic-mediated cerebral hypoperfusion 3).


Hu et al. investigated the therapeutic effects of SGB in a rat model of subarachnoid hemorrhage (SAH) complicated by delayed CVS and explore the underlying mechanisms. The SAH model was established by the double injection of autologous arterial blood into the cisterna magna. They simulated SGB by transection of the cervical sympathetic trunk (TCST), and measured changes in the diameter, perimeter, and cross-sectional area of the basilar artery (BA) and middle cerebral artery (MCA) to evaluate its vasodilatory effect. To investigate the underlying mechanisms, we determined the expression level of vasoactive molecules endothelin-1 (ET-1) and calcitonin gene-related peptide (CGRP) in the plasma, and apoptotic modulators Bcl-2 and Bax in the hippocampus. We found a significant increase in the diameter, perimeter, and cross-sectional area of the BA and right MCA in SAH rats subjected to TCST. Application of SGB significantly reduced the expression of ET-1 while increasing that of CGRP in SAH rats. We also found a significant increase in the expression of Bcl-2 and a decrease in the expression of Bax in the hippocampus of SAH rats subjected to TCST, when compared to untreated SAH rats. The mechanism of action of SGB is likely mediated through alterations in the ratio of ET-1 and CGRP, and Bax and Bcl-2. These results suggest that SGB can alleviate the severity of delayed CVS by inducing dilation of intracerebral blood vessels, and promoting anti-apoptotic signaling. Our findings provide evidence supporting the use of SGB as an effective and well-tolerated approach to the treatment of CVS in various clinical settings 4)


After successful modeling of cervical sympathetic block, 18 healthy male white rabbits were randomly divided into three groups (n=6), ie, sham operation group (Group A), SAH group (Group B) and SAH with cervical sympathetic block group (Group C). Models of delayed CVS were established by puncturing cisterna magna twice with an injection of autologous arterial blood in Groups B and C. A sham injection of blood through cisterna magna was made in Group A. 0.5 ml saline was injected each time through a catheter for cervical sympathetic block after the first injection of blood three times a day for 3 d in Group B (bilateral alternating). 0.5 ml of 0.25% bupivacaine was injected each time through a catheter for cervical sympathetic block after the first injection of blood three times a day for 7 d in Group B. 2 ml venous blood and cerebrospinal fluid were obtained before (T1), 30 min (T2) and 7 d (T3) after the first injection of blood, respectively, and conserved in a low temperature refrigerator. Basilar artery value at T1, T2 and T3 was measured via cerebral angiography. The degree of damage to nervous system at T1 and T3 was recorded.

Results: There was no significant difference in diameter of basilar artery at T1 among three groups. The diameters of basilar artery at T2 and T3 of Groups B and C were all smaller than that in Group A, which was smaller than Group C, with a significant difference. There was no significant difference in NO and NOS in plasma and cerebrospinal fluid among three groups. The NO and NOS contents at T2 and T3 of Groups B and C were all lower than Group A; Group C was higher than Group B, with a significant difference. The nerve function at T3 of Groups B and C were all lower than Group A and that of Group C higher than Group B, with a significant difference.

Cervical sympathetic block can relieve cerebral vasospasm after subarachnoid hemorrhage and increase NO content and NOS activity in plasma and cerebrospinal fluid to promote neural functional recovery 5)


1) , 3)

Kim WJ, Dacey M, Samarage HM, Zarrin D, Goel K, Chan C, Qi X, Wang AC, Shivkumar K, Ardell J, Colby GP. Sympathetic nervous system hyperactivity results in potent cerebral hypoperfusion in swine. Auton Neurosci. 2022 Sep;241:102987. doi: 10.1016/j.autneu.2022.102987. Epub 2022 May 6. PMID: 35567916; PMCID: PMC9659432.
2)

Bombardieri AM, Albers GW, Rodriguez S, Pileggi M, Steinberg GK, Heit JJ. Percutaneous cervical sympathetic block to treat cerebral vasospasm and delayed cerebral ischemia: a review of the evidence. J Neurointerv Surg. 2022 Dec 6:jnis-2022-019838. doi: 10.1136/jnis-2022-019838. Epub ahead of print. PMID: 36597947.
4)

Hu N, Wu Y, Chen BZ, Han JF, Zhou MT. Protective effect of stellate ganglion block on delayed cerebral vasospasm in an experimental rat model of subarachnoid hemorrhage. Brain Res. 2014 Oct 17;1585:63-71. doi: 10.1016/j.brainres.2014.08.012. Epub 2014 Aug 13. PMID: 25128600.
5)

Chun-jing H, Shan O, Guo-dong L, Hao-xiong N, Yi-ran L, Ya-ping F. Effect of cervical sympathetic block on cerebral vasospasm after subarachnoid hemorrhage in rabbits. Acta Cir Bras. 2013 Feb;28(2):89-93. doi: 10.1590/s0102-86502013000200001. PMID: 23370920.

Delirium Diagnosis

Delirium Diagnosis


Unlike dementiadelirium has an acute onset, motor signs (tremormyoclonusasterixis), slurred speech, altered consciousness (hyperalert/agitated or lethargic, or fluctuations), hallucinations may be florid.

Consultation-liaison psychiatry could improve the recognition rate of postoperative delirium in elderly patients, and shorten hospitalization time. The training of mental health knowledge for non-psychiatrists could improve the ability of early identify and treatment of delirium 1).


It is a corollary of the criteria that a diagnosis of delirium usually cannot be made without a previous assessment, or knowledge, of the affected person’s baseline level of cognitive function. In other words, a mentally disabled person who is suffering from this will be operating at their own baseline level of mental ability and would be expected to appear delirious without a baseline mental functional status against which to compare.

Early detection is crucial because the longer a patient experiences delirium the worse it becomes and the harder it is to treat. Currently, identification is through intermittent clinical assessment using standardized tools, like the Confusion Assessment Method for the Intensive Care Unit. Such tools work well in clinical research but do not translate well into clinical practice because they are subjective, intermittent, and have low sensitivity. As such, healthcare providers using these tools fail to recognize delirium symptoms as much as 80% of the time.

EEG shows pronounced diffuse slowing.

Delirium-related biochemical derangement leads to electrical changes in electroencephalographic (EEG) patterns followed by behavioral signs and symptoms. However, continuous EEG monitoring is not feasible due to the cost and the need for skilled interpretation. Studies using limited-lead EEG show large differences between patients with and without delirium while discriminating delirium from other causes. The Ceribell is a limited-lead device that analyzes EEG. If it is capable of detecting delirium, it would provide an objective physiological monitor to identify delirium before symptom onset. This pilot study was designed to explore relationships between Ceribell and delirium status. Completion of this study will provide a foundation for further research regarding delirium status using the Ceribell data 2).


Hut SC, Dijkstra-Kersten SM, Numan T, Henriquez NR, Teunissen NW, van den Boogaard M, Leijten FS, Slooter AJ. EEG and clinical assessment in delirium and acute encephalopathy. Psychiatry Clin Neurosci. 2021 May 16. doi: 10.1111/pcn.13225. Epub ahead of print. PMID: 33993579.


Early neutrophil-to-lymphocyte ratio (NLR) elevation may also predict delayed-onset delirium, potentially implicating systemic inflammation as a contributory delirium mechanism 3).

Older age, headache, coagulopathy, decreased level of consciousness, seizures, and history of falls. Conversely, infection was associated with a reduced yield.

In higher-risk patients and settings, there should be a push toward earlier neuroimaging as indicated by clinical examinations and individual risk factors. In the meta-analysis, the yield of head CT was higher in ICU patients and those who had focal neurological deficits in addition to altered mental status and was especially high in neuro ICU settings 4)

Neuroimaging should not replace a clinical exam, even in ICU settings; ICU patients should have their sedation reduced to properly test for delirium 5).

Delirium has a complex and fluctuating course with underlying causes that are often multifactorial; identifying a CNS lesion does not necessarily exclude other causes, and vice-versa 6).

The risks of neuroimaging need to be considered in the decision-making process 7).

The use of CT head to diagnose the etiology of delirium and AMS varied widely and yield has declined. Guidelines and clinical decision support tools could increase the appropriate use of CT head in the diagnostic etiology of delirium/AMS 8).


1)

Xie Q, Liu XB, Jing GW, Jiang X, Liu H, Zhong BL, Li Y. The Effect of Consultation-Liaison Psychiatry on Postoperative Delirium in Elderly Hip Fracture Patients in the General Hospital. Orthop Surg. 2023 Jan 3. doi: 10.1111/os.13501. Epub ahead of print. PMID: 36597675.
2)

Mulkey MA, Hardin SR, Munro CL, Everhart DE, Kim S, Schoemann AM, Olson DM. Methods of identifying delirium: A research protocol. Res Nurs Health. 2019 May 30. doi: 10.1002/nur.21953. [Epub ahead of print] PubMed PMID: 31148216.
3)

Reznik ME, Kalagara R, Moody S, Drake J, Margolis SA, Cizginer S, Mahta A, Rao SS, Stretz C, Wendell LC, Thompson BB, Asaad WF, Furie KL, Jones RN, Daiello LA. Common biomarkers of physiologic stress and associations with delirium in patients with intracerebral hemorrhage. J Crit Care. 2021 Mar 23;64:62-67. doi: 10.1016/j.jcrc.2021.03.009. Epub ahead of print. PMID: 33794468.
4)

MadsenTE, KhouryJ, Cadena R, et al. Potentially missed diagnosis of ischemic stroke in the Emergency Department in the Greater Cincinnati/Northern Kentucky stroke study.Acad Emerg Med. 2016;23(10):1128-1135. doi:10.1111/acem.13029
5)

Venkat A, Cappelen-Smith C, Askar S, et al. Factors associated with stroke misdiagnosis in the emergency department: a retrospective case-control study. Neuroepidemiology. 2018;51(3–4):123-127. doi:10.1159/000491635
6)

The 2019 American Geriatrics Society Beers Criteria®UpdateExpert Panel. American Geriatrics Society 2019 updated AGSbeers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67(4):674-694. doi:10.1111/jgs.15767
7)

Reznik ME, Rudolph JL. “Yield” to the time-brain dilemma: The case for neuroimaging in delirium. J Am Geriatr Soc. 2023 Jan 6. doi: 10.1111/jgs.18206. Epub ahead of print. PMID: 36606371.
8)

Akhtar H, Chaudhry SH, Bortolussi-Courval É, Hanula R, Akhtar A, Nauche B, McDonald EG. Diagnostic yield of CT head in delirium and altered mental status-A systematic review and meta-analysis. J Am Geriatr Soc. 2022 Nov 26. doi: 10.1111/jgs.18134. Epub ahead of print. PMID: 36434820.

Linezolid in Neurosurgery

Linezolid in Neurosurgery

Relevant studies were identified through searches of the PubMed, Current Contents, and Cochrane databases (publications archived until October 2006).

Case reports, case series, prospective and retrospective studies, and randomized controlled trials were eligible for inclusion in our review if they evaluated the effectiveness and safety of linezolid for the treatment of patients with CNS infections.

In 18 (42.9%) of the 42 relevant cases identified, patients had undergone neurosurgical operations and/or had prosthetic devices. Meningitis was the most common CNS infection, accounting for 20 (47.6%) cases. Other CNS infections included brain abscesses (14; 33.3%), ventriculitis (5; 11.9%), and ventriculo-peritoneal shunt infection (3; 7.1%). In the 39 patients in whom the responsible pathogen was isolated, those predominantly responsible for the CNS infections were: penicillin-nonsusceptible Streptococcus pneumoniae (7; 17.9%), vancomycin-resistant enterococci (6; 15.4%), Nocardia spp. (5; 12.8%), methicillin-resistant Staphylococcus epidermidis (4; 10.3%), and methicillin-resistant Staphylococcus aureus (3; 7.7%). Of the 42 patients who received linezolid for the treatment of CNS infections, 38 (90.5%) were either cured or showed clinical improvement of the infection. The mean duration of follow-up was 7.2 months; no recurrent CNS infection was reported.

The limited published data suggest that linezolid may be considered for the treatment of patients with CNS infections in cases of failure of previously administered treatment or limited available options 2).

To evaluate the efficacy and safety of SAT with oral linezolid in patients with NSI and to analyse the cost implications, an observational, non-comparative, prospective cohort study was conducted on clinically stable consecutive adult patients at the Neurosurgical Service. Following intravenous treatment, patients were discharged with SAT with oral linezolid.

A total of 77 patients were included. The most common NSIs were: 41 surgical wound infections, 20 subdural empyemas, 18 epidural abscesses, and 16 brain abscesses. Forty-four percent of patients presented two or more concomitant NSIs. Aetiological agents commonly isolated were: Propionibacterium acnes (36 %), Staphylococcus aureus (23 %), Staphylococcus epidermidis (21 %) and Streptococcus spp. (13 %). The median duration of the SAT was 15 days (range, 3-42). The SAT was interrupted in five cases due to adverse events. The remainder of the patients were cured at the end of the SAT. A total of 1,163 days of hospitalisation were saved. An overall cost reduction of €516,188 was attributed to the SAT. Eight patients with device infections did not require removal of the device, with an additional cost reduction of €190,595. The mean cost saving per patient was €9,179.

SAT with linezolid was safe and effective for the treatment of NSI. SAT reduces hospitalisation times, which means significant savings of health and economic resources 3).


Seventeen patients were included in the study. The main comorbidities among these patients included one or more of the following: subarachnoidal or intraventricular hemorrhage (n=8), solid neurological cancer (n=7), corticosteroids(n=9), and hydrocephalus (n=6). Eight patients underwent a craniotomy and fourteen patients had external ventricular drainage (EVD) as a predisposing factor for infection. Meningitis was the most common infection (11; 64.7%), followed by ventriculitis (4; 23.5%) and brain abscesses (2;11.8%). The main causative organisms were coagulase-negative Staphylococcus spp. (13; 76.5%). Linezolid was used as the initial therapy in 8 episodes, after therapy failure in 6, and for other reasons in 3. The oral route was used in 9 (52.9%) episodes; linezolid was initiated orally in 2 cases. The mean duration of treatment was 26.5 days (range 15-58). No adverse events were reported. Sixteen (94.1%) patients were considered cured. There was one recurrence. The mean length of hospital stay was 45.6 (range 15-112) days and the mean duration of follow-up was 7.2 (range 0.4-32) months. No related deaths occurred during active episodes.

Linezolid was mainly indicated in post-neurosurgical EVD-associated infections due to coagulase-negative Staphylococcus spp. It was used as initial therapy in most cases. A high rate of clinical cure was observed and no related adverse events were reported. More than half of the patients benefited from the advantages of the oral route of administration 4).


In order to study the penetration of this antimicrobial into the cerebrospinal fluid (CSF) of such patients, the disposition of linezolid in serum and CSF was studied in 14 neurosurgical patients given linezolid at 600 mg twice daily (1-h intravenous infusion) for the treatment of CNS infections caused by gram-positive pathogens or for prophylactic chemotherapy. Serum and CSF linezolid steady-state concentrations were analyzed by high-pressure liquid chromatography, and the concentration-time profiles obtained were analyzed to estimate pharmacokinetic parameters. The mean +/- standard deviation (SD) linezolid maximum and minimum measured concentrations were 18.6 +/- 9.6 microg/ml and 5.6 +/- 5.0 microg/ml, respectively, in serum and 10.8 +/- 5.7 microg/ml and 6.1 +/- 4.2 microg/ml, respectively, in CSF. The mean +/- SD areas under the concentration-time curves (AUCs) were 128.7 +/- 83.9 microg x h/ml for serum and 101.6 +/- 59.6 microg x h/ml for CSF, with a mean penetration ratio for the AUC for CSF to the AUC for serum of 0.66. The mean elimination half-life of linezolid in CSF was longer than that in serum (19.1 +/- 19.0 h and 6.5 +/- 3.6 h, respectively). The serum and CSF linezolid concentrations exceeded the pharmacodynamic breakpoint of 4 microg/ml for susceptible target pathogens for the entire dosing interval in the majority of patients. These findings suggest that linezolid may achieve adequate concentrations in the CSF of patients requiring antibiotics for the management or prophylaxis of CNS infections caused by gram-positive pathogens 5).


1)

Jahoda D, Nyc O, Pokorný D, Landor I, Sosna A. [Linezolid in the treatment of antibiotic-resistant gram-positive infections of the musculoskeletal system]. Acta Chir Orthop Traumatol Cech. 2006 Oct;73(5):329-33. Czech. PubMed PMID: 17140514.
2)

Ntziora F, Falagas ME. Linezolid for the treatment of patients with central nervous system infection. Ann Pharmacother. 2007 Feb;41(2):296-308. Epub 2007 Feb 6. Review. PubMed PMID: 17284501.
3)

Martín-Gandul C, Mayorga-Buiza MJ, Castillo-Ojeda E, Gómez-Gómez MJ, Rivero-Garvía M, Gil-Navarro MV, Márquez-Rivas FJ, Jiménez-Mejías ME. Sequential antimicrobial treatment with linezolid for neurosurgical infections: efficacy, safety and cost study. Acta Neurochir (Wien). 2016 Oct;158(10):1837-43. doi: 10.1007/s00701-016-2915-0. Epub 2016 Aug 13. PubMed PMID: 27520361.
4)

Sousa D, Llinares P, Meijide H, Gutiérrez JM, Miguez E, Sánchez E, Castelo L, Mena A. Clinical experience with linezolid for the treatment of neurosurgical infections. Rev Esp Quimioter. 2011 Mar;24(1):42-7. PMID: 21412669.
5)

Myrianthefs P, Markantonis SL, Vlachos K, Anagnostaki M, Boutzouka E, Panidis D, Baltopoulos G. Serum and cerebrospinal fluid concentrations of linezolid in neurosurgical patients. Antimicrob Agents Chemother. 2006 Dec;50(12):3971-6. doi: 10.1128/AAC.00051-06. Epub 2006 Sep 18. PMID: 16982782; PMCID: PMC1694012.

Frontal sinus cranialization

Frontal sinus cranialization


Cranialization refers to the removal of the posterior table of the frontal sinus with occlusion of the inlet into the frontonasal ducts and allowing the neural structures, mainly frontal lobes of the brain and the intact dura, to move directly posterior to the anterior table of the frontal bone 1).

Frontal sinus cranialization with closure via bifrontal pericranial flaps is the gold standard for separating the nasofrontal recess from the intracranial cavity for posterior table defects. Despite the high success rate, cerebrospinal fluid (CSF) leak may persist and is particularly challenging when vascularized reconstructive options from the bicoronal incision are exhausted.

For appropriately selected patients with extensive frontal injuries, cranialization is a procedure that provides an excellent margin of long-term safety and a satisfactory esthetic outcome. Individual surgeons will continue to differ at times as to the appropriate management of a particular frontal injury. Nevertheless, for the most severe of these, cranialization continues to be the definitive treatment 2).


In the case series of Donath and Sindwani indications included extensive frontal sinus fractures involving the posterior table (78.9%), mucocele (10.5%), arteriovenous malformation (5.3%), and frontal bone osteomyelitis (5.3%). 3).


For Calis et al. it seems that isolated anterior table fractures with a maximum amount of displacement of less than 4.5 mm can be treated conservatively without leading to contour deformities. CSF leakage in the acute setting might not always require cranialization and this may spontaneously resolve within 10 days. Cranialization should be considered whenever CSF leakage lasts longer than 10 days 4).


For Echo et al. the first step in assessing frontal sinus fractures involves the assessment of the posterior table of the frontal sinus and determining the need for cranialization. Criteria for cranialization include severe posterior table fracture, CSF leak greater than 1 to 2 weeks, or in any situation where a craniotomy is otherwise indicated. Any patient who meets these criteria would undergo a cranialization of the frontal sinus, obliteration of the nasofrontal outflow tracts, and reconstruction of the anterior table 5).


Using a pedicle vascularized pericranial flap as an extra layer and an autologous fence above the dura adds more protection to the brain. This flap may reduce the risk of CSF leak and perioperative infections and improve the overall results. Yet, more prospective and randomized trials are recommended 6).


Cranialization of the frontal sinus appears to be a good option for the prevention of secondary mucocele development after open excision of benign frontal sinus lesions 7).

A retrospective review of 3 patients (all male; ages 42, 43, and 69 yr) with persistent CSF leak despite frontal sinus cranialization and repair with bifrontal pericranium was performed. Etiology of injury was traumatic in 2 patients and iatrogenic in 1 patient after anaplastic meningioma treatment. To create space for the flap and repair the nasofrontal ducts, endoscopic Draf III (Case 1, 3) or Draf IIb left frontal sinusotomy (Case 2) was performed. The forearm flap was harvested, passed through a Caldwell-Luc exposure, and placed within the Draf frontal sinustomy. The flap vessels were tunneled to the left neck and anastomosed to the facial vessels by the mandibular notch.

Intraoperatively, the flaps were well-seated and provided a watertight seal. Postoperative hospital courses were uncomplicated. There were no new CSF leaks or flap necrosis at 12, 14, and 16 mo.

Endoscopic endonasal free flap reconstruction through a Draf procedure is a novel viable option for persistent CSF leak after failed frontal sinus cranialization 8).


Soto et al. presented the outcome data from 28 cases of frontal sinus trauma due to gunshot wounds. There was a statistically significant difference (P = 0.049) in the type reconstructive strategy employed with each type of flap, with pericranial flaps primarily used in cranialization, temporal grafts were more likely to be used in obliteration, and free flaps were more likely to be used in cranialization. The overall major complication rate was 52% (P = 0.248), with the most common acute major complication being cerebrospinal fluid leak (39%) and the major chronic was an abscess (23.5%).

This report explores the management of frontal sinus trauma and presents short-term outcomes of treatment for penetrating gunshot wounds at a tertiary referral center 9).


Shin et al. suggested a combination flap of galea and reverse temporalis muscle as a method for reconstruction of huge skull base defect.

From 2016 to 2019, a retrospective review was conducted, assessing 7 patients with bone defect which is not just opening of frontal sinus but extends to frontal sinus and cribriform plate. Reconstructions were done by combination of galeal flap and reverse temporalis muscle flap transposition.

Defects were caused by nasal cavity tumor with intracranial extension or brain tumor with nasal cavity extension. There was no major complication in every case. During the follow up period, no patient had signs of complication such as ascending infection, herniation and CSF rhinorrhea. Postoperative radiologic images of all patients that were taken at least 6 months after the surgery showed that flaps maintained the lining and the volume well.

Conventional reconstruction of skull base defect with galeal flap is not effective enough to cover the large sized defect. In conclusion, galeal flap in combination with reverse temporalis muscle flap can effectively block the communication of nasal cavity and intracranium 10).


19 patients underwent (bilateral) frontal sinus cranialization with the pericranial flap between 2000 and 2005. Indications included extensive frontal sinus fractures involving the posterior table (78.9%), mucocele (10.5%), arteriovenous malformation (5.3%), and frontal bone osteomyelitis (5.3%). There were no intraoperative complications. A postoperative cerebrospinal fluid leak occurred in one patient with extensive skull base injuries. This was repaired endoscopically. Follow-up ranged from 9 to 55 months.

The pericranial flap is easily harvested and versatile. Using this vascularized tissue during cranialization affords added protection by providing an extra barrier between the intracranial cavity and the frontal bone and sinonasal tract. This technique is inexpensive, safe, and effective and should be considered when cranialization of the frontal sinus is performed 11).

A 47-year-old man with adenoid cystic carcinoma who underwent secondary reconstruction of the frontal bone with a split-iliac crest bone flap based on the deep circumflex iliac artery. The patient’s course following an initial ablative procedure was complicated by recurrent periorbital cellulitis, radiation, and eventual recurrence of the malignancy. Reconstructive requirements included restoration of the superior orbital rim, cranialization of the frontal sinus, and reconstruction of a sizeable frontal bone defect. In this setting, the iliac crest served as an excellent reconstructive option owing to its natural curvature and large surface area. The split-iliac crest deep circumflex iliac artery bone flap offers a robust and valuable reconstructive option for calvarial defects in hostile surgical fields 12).


2)

Ruggiero, F. P., & Zender, C. A. (2010). Frontal sinus cranialization. Operative Techniques in Otolaryngology-Head and Neck Surgery, 21(2), 143-146. https://doi.org/10.1016/j.otot.2010.03.001
3) , 11)

Donath A, Sindwani R. Frontal sinus cranialization using the pericranial flap: an added layer of protection. Laryngoscope. 2006 Sep;116(9):1585-8. doi: 10.1097/01.mlg.0000232514.31101.39. PMID: 16954984.
4)

Calis M, Kaplan GO, Küçük KY, Altunbulak AY, Akgöz Karaosmanoğlu A, Işıkay Aİ, Mavili ME, Tunçbilek G. Algorithms for the management of frontal sinus fractures: A retrospective study. J Craniomaxillofac Surg. 2022 Oct 4:S1010-5182(22)00144-5. doi: 10.1016/j.jcms.2022.09.007. Epub ahead of print. PMID: 36220677.
5)

Echo A, Troy JS, Hollier LH Jr. Frontal sinus fractures. Semin Plast Surg. 2010 Nov;24(4):375-82. doi: 10.1055/s-0030-1269766. PubMed PMID: 22550461; PubMed Central PMCID: PMC3324222.
6)

Hammad W, Mahmoud B, Alsharif S. Frontal sinus cranialization using pericranial flap: Experience in thirty cases. Saudi J Otorhinolaryngol Head Neck Surg 2021;23:55-9
7)

Horowitz G, Amit M, Ben-Ari O, Gil Z, Abergel A, Margalit N, et al. (2013) Cranialization of the Frontal Sinus for Secondary Mucocele Prevention following Open Surgery for Benign Frontal Lesions. PLoS ONE 8(12): e83820. https://doi.org/10.1371/journal.pone.0083820
8)

Lee JJ, Wick EH, Chicoine MR, Dowling JL, Leuthardt EC, Santiago P, Pipkorn P. Endonasal Free Flap Reconstruction Combined With Draf Frontal Sinusotomy for Complex Cerebrospinal Fluid Leak: A Technical Report & Case Series. Oper Neurosurg (Hagerstown). 2021 Nov 15;21(6):478-484. doi: 10.1093/ons/opab309. PMID: 34423844; PMCID: PMC8599085.
9)

Soto E, Ovaitt AK, Clark AR, Tindal RR, Chiasson KF, Aryanpour Z, Ananthasekar S, Grant JH, Myers RP. Reconstructive Management of Gunshot Wounds to the Frontal Sinus: An Urban Trauma Center’s Perspective. Ann Plast Surg. 2021 Jun 1;86(6S Suppl 5):S550-S554. doi: 10.1097/SAP.0000000000002857. PMID: 33883442; PMCID: PMC8187270.
10)

Shin D, Yang CE, Kim YO, Hong JW, Lee WJ, Lew DH, Chang JH, Kim CH. Huge Anterior Skull Base Defect Reconstruction on Communicating Between Cranium and Nasal Cavity: Combination Flap of Galeal Flap and Reverse Temporalis Flap. J Craniofac Surg. 2020 Feb 7. doi: 10.1097/SCS.0000000000006221. [Epub ahead of print] PubMed PMID: 32049922.
12)

Baudoin ME, Palines PA, Stalder MW. Frontal Cranioplasty with Vascularized Split-iliac Crest Bone Flap. Plast Reconstr Surg Glob Open. 2021 Nov 16;9(11):e3934. doi: 10.1097/GOX.0000000000003934. PMID: 34796087; PMCID: PMC8594656.

ShuntScope

ShuntScope

Autoclavable reusable SHUNTSCOPE® is designed to facilitate the endoscopic ventricular drainage placement during shunt surgery.

A retrospective analysis of all pediatric patients undergoing ventricular catheter placement using the ShuntScope from 01/2012 to 01/2022 in the Department of Neurosurgery, Saarland University Medical Center, Homburg was performed. Demographic, clinical, and radiological data were evaluated. The visualization quality of the intraoperative endoscopy was stratified into the categories of excellent, medium, and poor and compared to the postoperative catheter tip placement. Follow-up evaluation included the surgical revision rate due to proximal catheter occlusion.

A total of 65 ShuntScope-assisted surgeries have been performed on 51 children. The mean age was 5.1 years. The most common underlying pathology was a tumor- or cyst-related hydrocephalus in 51%. Achieved image quality was excellent in 41.5%, medium in 43%, and poor in 15.5%. Ideal catheter placement was achieved in 77%. There were no intraoperative ventricular catheter placement complications and no technique-related morbidity associated with the ShuntScope. The revision rate due to proximal occlusion was 4.61% during a mean follow-up period of 39.7 years. No statistical correlation between image grade and accuracy of catheter position was observed (p-value was 0.290).

The ShuntScope can be considered a valuable addition to standard surgical tools in pediatric hydrocephalus treatment. Even suboptimal visualization contributes to high rates of correct catheter placement and, thereby, to a favorable clinical outcome 1).


The purpose of the study is to compare the accuracy of catheter placement and the complication and revision rates between SG and freehand (FH) techniques.

A retrospective study based on a prospectively acquired database of patients who underwent VC placement between September 2018 and July 2021. The accuracy of catheter placement was graded on postoperative imaging using a three-point Hayhurst grading system. Complication and revision rates were documented and compared between both groups with an average follow-up period of 20.84 months.

Results: Fifty-seven patients were included. SG technique was used in 29 patients (mean age was 6.3 years, 1.4 -27.7 years, 48.1% females), and FH technique was used in 28 patients (mean age was 26.7 years, 0.83 – 79.5 years, 67.9% female). The success rate for the optimal placement of the VC with a grade I on the Hayhurst scale was significantly higher in the SG group (93.1%) than in the FH group (60.7%), P = 0.012. The revision rate was higher in the FH group with 35.7% vs. 20.7% of in the SG group, P = 0.211.

Conclusion: VC placement using the SG technique is a safe and effective procedure, which enabled a significantly higher success rate and lower revision and complication rate. Accordingly, we recommend using the SG technique especially in patients with difficult anatomy 2)


The experience of shuntscope-guided ventriculoperitoneal shunt in 9 cases done from June 2015 to April 2016. Shuntscope is a 1 mm outer diameter semi-rigid scope from Karl Storz with 10000 pixels of magnification. It has a fiber optic lens system with a camera and light source attachment away from the scope to make it lightweight and easily maneuverable.

Results: In all cases, VC was placed in the ipsilateral frontal horn away from choroid plexuses, septae, or membranes. Septum pellucidum perforation and placement to the opposite side of the ventricle was identified with shunt scope assistance and corrected.

Conclusion: Although our initial results are encouraging, larger case series would be helpful. Complications and cost due to shunt dysfunction can thus be reduced to a great extent with shuntscope 3)


The semi-rigid ShuntScope (Karl Storz GmbH & Co.KG, Tuttlingen, Germany) with an outer diameter of 1.0 mm and an image resolution of 10,000 pixels was used in a series of 27 children and adolescents (18 males, 9 females, age range 2 months-18 years). Indications included catheter placement in aqueductal stenting (n = 4), first-time shunt placement (n = 5), burr hole reservoir insertion (n = 4), catheter placement after endoscopic procedures (n = 7) and revision surgery of the ventricle catheter (n = 7).

ShuntScope-guided precise catheter placement was achieved in 26 of 27 patients. In one case of aqueductal stenting, the procedure had to be abandoned. One single wound healing problem was noted as a complication. Intraventricular image quality was always sufficient to recognize the anatomical structures. In the case of catheter removal, it was helpful to identify adherent vessels or membranes. Penetration of small adhesions or thin membranes was feasible. Postoperative imaging studies demonstrated catheter tip placements analogous to the intraoperative findings.

Misplacements of shunt catheters are completely avoidable with the presented intra-catheter technique including slit ventricles or even aqueductal stenting. Potential complications can be avoided during revision surgery. The implementation of the ShuntScope is recommended in pediatric neurosurgery 4).


1)

Prajsnar-Borak A, Teping F, Oertel J. Image quality and related outcomes of the ShuntScope for catheter implantation in pediatric hydrocephalus-experience of 65 procedures. Childs Nerv Syst. 2022 Dec 2. doi: 10.1007/s00381-022-05776-1. Epub ahead of print. PMID: 36459211.
2)

Issa M, Nofal M, Miotik N, Seitz A, Unterberg A, El Damaty A. ShuntScope®-Guided Versus Free Hand Technique for Ventricular Catheter Placement: A Retrospective Comparative Study of Intra-Ventricular Catheter Tip Position and Complication Rate. J Neurol Surg A Cent Eur Neurosurg. 2022 Feb 10. doi: 10.1055/a-1768-3892. Epub ahead of print. PMID: 35144299.
3)

Agrawal V, Aher RB. Endoluminal Shuntscope-Guided Ventricular Catheter Placement: Early Experience. Asian J Neurosurg. 2018 Oct-Dec;13(4):1071-1073. doi: 10.4103/ajns.AJNS_98_17. PMID: 30459870; PMCID: PMC6208226.
4)

Senger S, Antes S, Salah M, Tschan C, Linsler S, Oertel J. The view through the ventricle catheter – The new ShuntScope for the therapy of pediatric hydrocephalus. J Clin Neurosci. 2018 Feb;48:196-202. doi: 10.1016/j.jocn.2017.10.046. Epub 2017 Nov 6. PubMed PMID: 29102235.