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Carlo Serra, Victor E. Staartjes, Nicolai Maldaner, David Holzmann, Michael B. Soyka, Marco Gilone, Christoph Schmid, Oliver Tschopp and Luca Regli

OBJECTIVE

The “chopsticks” technique is a 3-instrument, 2-hand mononostril technique that has been recently introduced in endoscopic neurosurgery. It allows a dynamic surgical view controlled by one surgeon only while keeping bimanual dissection. Being a mononostril approach, it requires manipulation of the mucosa of one nasal cavity only. The rationale of the technique is to reduce nasal morbidity without compromising surgical results and complication rates. There are, however, no data available on its results in endoscopic surgery (transsphenoidal surgery [TSS]) for pituitary adenoma.

METHODS

The authors performed a cohort analysis of prospectively collected data on 144 patients (156 operations) undergoing TSS using the chopsticks technique with 3T intraoperative MRI. All patients had at least 3 months of postoperative neurosurgical, endocrinological, and rhinological follow-up (Sino-Nasal Outcome Test–20 [SNOT-20] and Sniffin’ Sticks). The surgical technique is described, and the achieved gross-total resection (GTR) and extent of resection (EOR) together with patients’ clinical outcomes and complications are descriptively reported.

RESULTS

On 3-month postoperative MRI, GTR was achieved in 71.2% of patients with a mean EOR of 96.7%. GTR was the surgical goal in 122 of 156 cases and was achieved in 106 of 122 (86.9%), with a mean EOR of 98.7% (median 100%, range 49%–100%). There was no surgical mortality. At a median follow-up of 15 months (range 3–70 months), there was 1 permanent neurological deficit. As of the last available follow-up, 11.5% of patients had a new pituitary single-axis deficit, whereas 26.3% had improvement in endocrinological function. Three patients had new postoperative hyposmia. One patient had severe impairment of sinonasal function (SNOT-20 score > 40). The operation resulted in endocrine remission in 81.1% of patients with secreting adenomas.

CONCLUSIONS

This study shows that the chopsticks technique confers resection and morbidity results that compare favorably with literature reports of TSS. This technique permits a single surgeon to perform effective endoscopic bimanual dissection through a single nostril, reducing manipulation of healthy tissue and thereby possibly minimizing surgical morbidity.

Free access

Martin N. Stienen, Nicolai Maldaner, Holger Joswig, Marco V. Corniola, David Bellut, Peter Prömmel, Luca Regli, Astrid Weyerbrock, Karl Schaller and Oliver P. Gautschi

OBJECTIVE

Patient-reported outcome measures (PROMs) are standard of care for the assessment of functional impairment. Subjective outcome measures are increasingly complemented by objective ones, such as the “Timed Up and Go” (TUG) test. Currently, only a few studies report pre- and postoperative TUG test assessments in patients with lumbar spinal stenosis (LSS).

METHODS

A prospective two-center database was reviewed to identify patients with LSS who underwent lumbar decompression with or without fusion. The subjective functional status was estimated using PROMs for pain (visual analog scale [VAS]), disability (Roland-Morris Disability Index [RMDI] and Oswestry Disability Index [ODI]), and health-related quality of life (HRQoL; 12-Item Short-Form Physical Component Summary [SF-12 PCS] and the EQ-5D) preoperatively, as well as on postoperative day 3 (D3) and week 6 (W6). Objective functional impairment (OFI) was measured using age- and sex-standardized TUG test results.

RESULTS

Sixty-four patients (n = 32 [50%] male, mean age 66.8 ± 11.7 years) were included. Preoperatively, they reported a mean VAS back pain score of 4.1 ± 2.7, VAS leg pain score of 5.4 ± 2.7, RMDI of 10.4 ± 5.3, ODI of 41.9 ± 16.2, SF-12 PCS score of 32.7 ± 8.3, and an EQ-5D index of 0.517 ± 0.226. The preoperative rates of severe, moderate, and mild OFI were 4.7% (n = 3), 12.5% (n = 8), and 7.8% (n = 5), respectively, and the mean OFI T-score was 116.3 ± 23.7. At W6, 60 (93.8%) of 64 patients had a TUG test result within the normal population range (no OFI); 3 patients (4.7%) had mild and 1 patient (1.6%) severe OFI. The mean W6 OFI T-score was significantly decreased (103.1 ± 13.6; p < 0.001). Correspondingly, the PROMs showed a decrease in subjective VAS back pain (1.6 ± 1.7, p < 0.001) and leg pain (1.0 ± 1.8, p < 0.001) scores, disability (RMDI 5.3 ± 4.7, p < 0.001; ODI 21.3 ± 16.1, p < 0.001), and increase in HRQoL (SF-12 PCS 40.1 ± 8.3, p < 0.001; EQ-5D 0.737 ± 0.192, p < 0.001) at W6. The W6 responder status (clinically meaningful improvement) ranged between 81.3% (VAS leg pain) and 29.7% (EQ-5D index) of patients.

CONCLUSIONS

The TUG test is a quick and easily applicable tool that reliably measures OFI in patients with LSS. Objective tests incorporating longer walking time should be considered if OFI is suspected but fails to be proven by the TUG test, taking into account that neurogenic claudication may not clinically manifest during the brief TUG examination. Objective tests do not replace the subjective PROM-based assessment, but add valuable information to a comprehensive patient evaluation.

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Victor E. Staartjes, Costanza M. Zattra, Kevin Akeret, Nicolai Maldaner, Giovanni Muscas, Christiaan Hendrik Bas van Niftrik, Jorn Fierstra, Luca Regli and Carlo Serra

OBJECTIVE

Although rates of postoperative morbidity and mortality have become relatively low in patients undergoing transnasal transsphenoidal surgery (TSS) for pituitary adenoma, cerebrospinal fluid (CSF) fistulas remain a major driver of postoperative morbidity. Persistent CSF fistulas harbor the potential for headache and meningitis. The aim of this study was to investigate whether neural network–based models can reliably identify patients at high risk for intraoperative CSF leakage.

METHODS

From a prospective registry, patients who underwent endoscopic TSS for pituitary adenoma were identified. Risk factors for intraoperative CSF leaks were identified using conventional statistical methods. Subsequently, the authors built a prediction model for intraoperative CSF leaks based on deep learning.

RESULTS

Intraoperative CSF leaks occurred in 45 (29%) of 154 patients. No risk factors for CSF leaks were identified using conventional statistical methods. The deep neural network–based prediction model classified 88% of patients in the test set correctly, with an area under the curve of 0.84. Sensitivity (83%) and specificity (89%) were high. The positive predictive value was 71%, negative predictive value was 94%, and F1 score was 0.77. High suprasellar Hardy grade, prior surgery, and older age contributed most to the predictions.

CONCLUSIONS

The authors trained and internally validated a robust deep neural network–based prediction model that identifies patients at high risk for intraoperative CSF. Machine learning algorithms may predict outcomes and adverse events that were previously nearly unpredictable, thus enabling safer and improved patient care and better patient counseling.

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Nicolai Maldaner, Marketa Sosnova, Anna M. Zeitlberger, Michal Ziga, Oliver P. Gautschi, Luca Regli, Astrid Weyerbrock, Martin N. Stienen and for the International 6WT Study Group

OBJECTIVE

Digital transformation enables new possibilities to assess objective functional impairment (OFI) in patients with lumbar degenerative disc disease (DDD). This study examines the psychometric properties of an app-based 6-minute walking test (6WT) and determines OFI in patients with lumbar DDD.

METHODS

The maximum 6-minute walking distance (6WD) was determined in patients with lumbar DDD. The results were expressed as raw 6WDs (in meters), as well as in standardized z-scores referenced to age- and sex-specific values of spine-healthy volunteers. The 6WT results were assessed for reliability and content validity using established disease-specific patient-reported outcome measures.

RESULTS

Seventy consecutive patients and 330 volunteers were enrolled. The mean 6WD was 370 m (SD 137 m) in patients with lumbar DDD. Significant correlations between 6WD and the Core Outcome Measures Index for the back (r = −0.31), Zurich Claudication Questionnaire (ZCQ) symptom severity (r = −0.32), ZCQ physical function (r = −0.33), visual analog scale (VAS) for back pain (r = −0.42), and VAS for leg pain (r = −0.32) were observed (all p < 0.05). The 6WT revealed good test-retest reliability (intraclass correlation coefficient 0.82), and the standard error of measurement was 58.3 m. A 4-tier severity stratification classified patients with z-scores > −1 (no OFI), −1 to −1.9 (mild OFI), −2 to −2.9 (moderate OFI), and ≤ −3 (severe OFI).

CONCLUSIONS

The smartphone app-based self-measurement of the 6WT is a convenient, reliable, and valid way to determine OFI in patients with lumbar DDD. The 6WT app facilitates the digital evaluation and monitoring of patients with lumbar DDD.

Free access

Victor E. Staartjes, Carlo Serra, Giovanni Muscas, Nicolai Maldaner, Kevin Akeret, Christiaan H. B. van Niftrik, Jorn Fierstra, David Holzmann and Luca Regli

OBJECTIVE

Gross-total resection (GTR) is often the primary surgical goal in transsphenoidal surgery for pituitary adenoma. Existing classifications are effective at predicting GTR but are often hampered by limited discriminatory ability in moderate cases and by poor interrater agreement. Deep learning, a subset of machine learning, has recently established itself as highly effective in forecasting medical outcomes. In this pilot study, the authors aimed to evaluate the utility of using deep learning to predict GTR after transsphenoidal surgery for pituitary adenoma.

METHODS

Data from a prospective registry were used. The authors trained a deep neural network to predict GTR from 16 preoperatively available radiological and procedural variables. Class imbalance adjustment, cross-validation, and random dropout were applied to prevent overfitting and ensure robustness of the predictive model. The authors subsequently compared the deep learning model to a conventional logistic regression model and to the Knosp classification as a gold standard.

RESULTS

Overall, 140 patients who underwent endoscopic transsphenoidal surgery were included. GTR was achieved in 95 patients (68%), with a mean extent of resection of 96.8% ± 10.6%. Intraoperative high-field MRI was used in 116 (83%) procedures. The deep learning model achieved excellent area under the curve (AUC; 0.96), accuracy (91%), sensitivity (94%), and specificity (89%). This represents an improvement in comparison with the Knosp classification (AUC: 0.87, accuracy: 81%, sensitivity: 92%, specificity: 70%) and a statistically significant improvement in comparison with logistic regression (AUC: 0.86, accuracy: 82%, sensitivity: 81%, specificity: 83%) (all p < 0.001).

CONCLUSIONS

In this pilot study, the authors demonstrated the utility of applying deep learning to preoperatively predict the likelihood of GTR with excellent performance. Further training and validation in a prospective multicentric cohort will enable the development of an easy-to-use interface for use in clinical practice.

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Michel Roethlisberger, Lara Gut, Daniel Walter Zumofen, Urs Fisch, Oliver Boss, Nicolai Maldaner, Davide Marco Croci, Ethan Taub, Natascia Corti, Jan-Karl Burkhardt, Raphael Guzman, Oliver Bozinov and Luigi Mariani

OBJECTIVE

Women taking combined hormonal contraceptives (CHCs) are generally considered to be at low risk for cerebral venous thrombosis (CVT). When it does occur, however, intensive care and neurosurgical management may, in rare cases, be needed for the control of elevated intracranial pressure (ICP). The use of nonsurgical strategies such as barbiturate coma and induced hypothermia has never been reported in this context. The objective of this study is to determine predictive factors for invasive or surgical ICP treatment and the potential complications of nonsurgical strategies in this population.

METHODS

The authors conducted a 2-center, retrospective chart review of 168 cases of CVT in women between 2000 and 2012. Eligible patients were classified as having had a mild or a severe clinical course, the latter category including all patients who underwent invasive or surgical ICP treatment and all who had an unfavorable outcome (modified Rankin Scale score ≥ 3 or Glasgow Outcome Scale score ≤ 3). The Mann-Whitney U-test was used for continuous parameters and Fisher’s exact test for categorical parameters, and odds ratios were calculated with statistical significance set at p ≤ 0.05.

RESULTS

Of the 168 patients, 57 (age range 16–49 years) were determined to be eligible for the study. Six patients (10.5%) required invasive or surgical ICP treatment. Three patients (5.3%) developed refractory ICP > 30 mm Hg despite early surgical decompression; 2 of them (3.5%) were treated with barbiturate coma and induced hypothermia, with documented infectious, thromboembolic, and hemorrhagic complications. Coma on admission, thrombosis of the deep venous system with consecutive hydrocephalus, intraventricular hemorrhage, and hemorrhagic venous infarction were associated with a higher frequency of surgical intervention. Coma, quadriparesis on admission, and hydrocephalus were more commonly seen among women with unfavorable outcomes. Thrombosis of the transverse sinus was less common in patients with an unfavorable outcome, with similar distribution in patients needing invasive or surgical ICP treatment.

CONCLUSIONS

The need for invasive or surgical ICP treatment in women taking CHCs who have CVT is partly predictable on the basis of the clinical and radiological findings on admission. The use of nonsurgical treatments for refractory ICP, such as barbiturate coma and induced hypothermia, is associated with systemic infectious and hematological complications and may worsen morbidity in this patient population. The significance of these factors should be studied in larger multicenter cohorts.

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Martin N. Stienen, Oliver P. Gautschi, Victor E. Staartjes, Nicolai Maldaner, Marketa Sosnova, Allen L. Ho, Anand Veeravagu, Atman Desai, Corinna C. Zygourakis, Jon Park, Luca Regli and John K. Ratliff

OBJECTIVE

Objective functional measures such as the 6-minute walking test (6WT) are increasingly applied to evaluate patients with degenerative diseases of the lumbar spine before and after (surgical) treatment. However, the traditional 6WT is cumbersome to apply, as it requires specialized in-hospital infrastructure and personnel. The authors set out to compare 6-minute walking distance (6WD) measurements obtained with a newly developed smartphone application (app) and those obtained with the gold-standard distance wheel (DW).

METHODS

The authors developed a free iOS- and Android-based smartphone app that allows patients to measure the 6WD in their home environment using global positioning system (GPS) coordinates. In a laboratory setting, the authors obtained 6WD measurements over a range of smartphone models, testing environments, and walking patterns and speeds. The main outcome was the relative measurement error (rME; in percent of 6WD), with |rME| < 7.5% defined as reliable. The intraclass correlation coefficient (ICC) for agreement between app- and DW-based 6WD was calculated.

RESULTS

Measurements (n = 406) were reliable with all smartphone types in neighborhood, nature, and city environments (without high buildings), as well as with unspecified, straight, continuous, and stop-and-go walking patterns (ICC = 0.97, 95% CI 0.97–0.98, p < 0.001). Measurements were unreliable indoors, in city areas with high buildings, and for predominantly rectangular walking courses. Walking speed had an influence on the ME, with worse accuracy (2% higher rME) for every kilometer per hour slower walking pace (95% CI 1.4%–2.5%, p < 0.001). Mathematical adjustment of the app-based 6WD for velocity-dependent error mitigated the rME (p < 0.011), attenuated velocity dependence (p = 0.362), and had a positive effect on accuracy (ICC = 0.98, 95% CI 0.98–0.99, p < 0.001).

CONCLUSIONS

The new, free, spine-specific 6WT smartphone app measures the 6WD conveniently by using GPS coordinates, empowering patients to independently determine their functional status before and after (surgical) treatment. Measurements of 6WD obtained for the target population under the recommended circumstances are highly reliable.

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Pavlina Lenga, Christian Hohaus, Bujung Hong, Adisa Kursumovic, Nicolai Maldaner, Jan-Karl Burkhardt, Philippe Bijlenga, Daniel A. Rüfenacht, Nils O. Schmidt, Peter Vajkoczy and Julius Dengler

OBJECTIVE

Giant posterior circulation aneurysms (GPCirAs) usually cause substantial mass effect on the brainstem, which may lead to neurological deficits. So far, there has been no systematic investigation of factors associated with such deficits in GPCirA. The authors aim to examine the risk factors for cranial nerve deficit (CND), motor deficit, and disability in patients with GPCirA.

METHODS

Using MR images obtained in 30 patients with unruptured GPCirA, the authors examined GPCirA volume, presence of hydrocephalus or partial thrombosis (PT) of the aneurysm, and the degree of brainstem displacement measured by the distance between the McRae line and the tip of the GPCirA (∆MT). They evaluated associations between these factors and neurological deficits.

RESULTS

Thirty GPCirAs in 30 patients were included. The prevalence of CNDs was 50%. Patients with CNDs significantly differed from those without CNDs in terms of age (mean 51.0 years [SD 15.0 years] vs 69.0 years [SD 21.0 years], p = 0.01) and in ∆MT (median 50.7 mm [IQR 39.2–53.9 mm] vs 39.0 mm [IQR 32.3–45.9 mm], p = 0.02). The prevalence of motor deficits was 33.3%. Patients with motor deficits showed a larger ∆MT (median 50.5 mm [IQR 40.8–54.6 mm]) compared with those without (∆MT: median 39.1 mm [IQR 32.8–50.5 mm], p = 0.04). GPCirA volume was larger in patients with poor modified Rankin Scale (mRS) scores (median 14.9 cm3 [IQR 8.6–18.7 cm3]) than in those with mRS scores of 0–2 (median 6.8 cm3 [IQR 4.4–11.7 cm3], p = 0.03). After adjusting for patient age and the occurrence of hydrocephalus or PT, the authors found that higher degrees of disability were significantly associated with aneurysm volume (OR 1.13, 95% CI 1.0–1.3; p = 0.04), but not with ∆MT. The occurrence of CND or motor deficit was not associated with any of the examined variables. There was no correlation between GPCirA volume and ∆MT (rs = 0.01, p = 0.96). The prevalence of neurological deficits did not differ between GPCirA at the basilar apex, the basilar trunk, the vertebrobasilar junction, or the vertebral artery.

CONCLUSIONS

In this study, the neurological condition of the patients was associated only with GPCirA volume and not with the degree of brainstem displacement, the occurrence of PT or hydrocephalus, or the exact location of the GPCirA. These findings highlight the clinical relevance of GPCirA volume and suggest that factors such as brainstem displacement or PT should play less of a role when finding arguments for or against treatment of GPCirA.

Clinical trial registration no.: NCT02066493 (clinicaltrials.gov)

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Lazar Tosic, Elior Goldberger, Nicolai Maldaner, Marketa Sosnova, Anna M. Zeitlberger, Victor E. Staartjes, Pravesh S. Gadjradj, Hubert A. J. Eversdijk, Ayesha Quddusi, Maria L. Gandía-González, Jamasb Joshua Sayadi, Atman Desai, Luca Regli, Oliver P. Gautschi and Martin N. Stienen

OBJECTIVE

The 6-minute walking test (6WT) is used to determine restrictions in a subject’s 6-minute walking distance (6WD) due to lumbar degenerative disc disease. To facilitate simple and convenient patient self-measurement, a free and reliable smartphone app using Global Positioning System coordinates was previously designed. The authors aimed to determine normative values for app-based 6WD measurements.

METHODS

The maximum 6WD was determined three times using app-based measurement in a sample of 330 volunteers without previous spine surgery or current spine-related disability, recruited at 8 centers in 5 countries (mean subject age 44.2 years, range 16–91 years; 48.5% male; mean BMI 24.6 kg/m2, range 16.3–40.2 kg/m2; 67.9% working; 14.2% smokers). Subjects provided basic demographic information, including comorbidities and patient-reported outcome measures (PROMs): visual analog scale (VAS) for both low-back and lower-extremity pain, Core Outcome Measures Index (COMI), Zurich Claudication Questionnaire (ZCQ), and subjective walking distance and duration. The authors determined the test-retest reliability across three measurements (intraclass correlation coefficient [ICC], standard error of measurement [SEM], and mean 6WD [95% CI]) stratified for age and sex, and content validity (linear regression coefficients) between 6WD and PROMs.

RESULTS

The ICC for repeated app-based 6WD measurements was 0.89 (95% CI 0.87–0.91, p < 0.001) and the SEM was 34 meters. The overall mean 6WD was 585.9 meters (95% CI 574.7–597.0 meters), with significant differences across age categories (p < 0.001). The 6WD was on average about 32 meters less in females (570.5 vs 602.2 meters, p = 0.005). There were linear correlations between average 6WD and VAS back pain, VAS leg pain, COMI Back and COMI subscores of pain intensity and disability, ZCQ symptom severity, ZCQ physical function, and ZCQ pain and neuroischemic symptoms subscores, as well as with subjective walking distance and duration, indicating that subjects with higher pain, higher disability, and lower subjective walking capacity had significantly lower 6WD (all p < 0.001).

CONCLUSIONS

This study provides normative data for app-based 6WD measurements in a multicenter sample from 8 institutions and 5 countries. These values can now be used as reference to compare 6WT results and quantify objective functional impairment in patients with degenerative diseases of the spine using z-scores. The authors found a good to excellent test-retest reliability of the 6WT app, a low area of uncertainty, and high content validity of the average 6WD with commonly used PROMs.

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Julius Dengler, Nicolai Maldaner, Philippe Bijlenga, Jan-Karl Burkhardt, Alexander Graewe, Susanne Guhl, Bujung Hong, Christian Hohaus, Adisa Kursumovic, Dorothee Mielke, Karl-Michael Schebesch, Maria Wostrack, Daniel Rufenacht, Peter Vajkoczy, Nils Ole Schmidt and Giant Intracranial Aneurysm Study Group

OBJECT

The underlying mechanisms causing intracranial perianeurysmal edema (PAE) are still poorly understood. Since PAE is most frequently observed in giant intracranial aneurysms (GIAs), the authors designed a study to examine the occurrence of PAE in relation to the location, size, and partial thrombosis (PT) of GIAs along with the clinical impact of PAE.

METHODS

Magnetic resonance imaging data for patients with a diagnosis of unruptured GIA from the international multicenter Giant Intracranial Aneurysm Registry were retrospectively analyzed with regard to location and size of the GIA, PAE volume, and the presence of PT. The occurrence of PAE was correlated to clinical findings.

RESULTS

Imaging data for 69 GIAs were eligible for inclusion in this study. Perianeurysmal edema was observed in 33.3% of all cases, with the highest frequency in GIAs of the middle cerebral artery (MCA; 68.8%) and the lowest frequency in GIAs of the cavernous internal carotid artery (ICA; 0.0%). Independent predictors of PAE formation were GIA volume (OR 1.13, p = 0.02) and the occurrence of PT (OR 9.84, p = 0.04). Giant intracranial aneurysm location did not predict PAE occurrence. Giant aneurysms with PAE were larger than GIAs without PAE (p < 0.01), and GIA volume correlated with PAE volume (rs = 0.51, p = 0.01). Perianeurysmal edema had no influence on the modified Rankin Scale score (p = 0.30 or the occurrence of aphasia (p = 0.61) or hemiparesis (p = 0.82).

CONCLUSIONS

Perianeurysmal edema was associated with GIA size and the presence of PT. As no PAE was observed in cavernous ICA aneurysms, even though they exerted mass effect on the brain and also displayed PT, the dura mater may serve as a barrier protecting the brain from PAE formation.