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## Anatomy of the L5 nerve root in the pelvis for safe sacral screw placement: a cadaveric study

### OBJECTIVE

Previous reports have focused on the complications of L5 nerve root injury caused by anterolateral misplacement of the S1 pedicle screws. Anatomical knowledge of the L5 nerve root in the pelvis is essential for safe and effective placement of the sacral screw. This cadaveric study aimed to investigate the course of the L5 nerve root in the pelvis and to clarify a safe zone for inserting the sacral screw.

### METHODS

Fifty-four L5 nerve roots located bilaterally in 27 formalin-fixed cadavers were studied. The ventral rami of the L5 nerve roots were dissected along their courses from the intervertebral foramina to the lesser pelvis. The running angles of the L5 nerve roots from the centerline were measured in the coronal plane. In addition, the distances from the ala of the sacrum to the L5 nerve roots were measured in the sagittal plane.

### RESULTS

The authors found that the running angles of the L5 nerve roots changed at the most anterior surface of the ala of the sacrum. The angles of the bilateral L5 nerve roots from the right and left L5 intervertebral foramina to their inflection points were 13.77° ± 5.01° and 14.65° ± 4.71°, respectively. The angles of the bilateral L5 nerve roots from the right and left inflection points to the lesser pelvis were 19.66° ± 6.40° and 20.58° ± 5.78°, respectively. There were no significant differences between the angles measured in the right and left nerve roots. The majority of the L5 nerves coursed outward after changing their angles at the inflection point. The distances from the ala of the sacrum to the L5 nerve roots in the sagittal plane were less than 1 mm in all cases, which indicated that the L5 nerve roots were positioned close to the ala of the sacrum and had poor mobility.

### CONCLUSIONS

All of the L5 nerve roots coursed outward after exiting the intervertebral foramina and never inward. To prevent iatrogenic L5 nerve root injury, surgeons should insert the S1 pedicle screw medially with an angle > 0° toward the inside of the S1 anterior foramina and the sacral alar screw laterally with an angle > 30°.

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## Anterior versus posterior entry site for ventriculoperitoneal shunt insertion: a randomized controlled trial by the Hydrocephalus Clinical Research Network

### OBJECTIVE

The primary objective of this trial was to determine if shunt entry site affects the risk of shunt failure.

### METHODS

The authors performed a parallel-design randomized controlled trial with an equal allocation of patients who received shunt placement via the anterior entry site and patients who received shunt placement via the posterior entry site. All patients were children with symptoms or signs of hydrocephalus and ventriculomegaly. Patients were ineligible if they had a prior history of shunt insertion. Patients received a ventriculoperitoneal shunt after randomization; randomization was stratified by surgeon. The primary outcome was shunt failure. The planned minimum follow-up was 18 months. The trial was designed to achieve high power to detect a 10% or greater absolute difference in the shunt failure rate at 1 year. An independent, blinded adjudication committee determined eligibility and the primary outcome. The study was conducted by the Hydrocephalus Clinical Research Network.

### RESULTS

The study randomized 467 pediatric patients at 14 tertiary care pediatric hospitals in North America from April 2015 to January 2019. The adjudication committee, blinded to intervention, excluded 7 patients in each group for not meeting the study inclusion criteria. For the primary analysis, there were 229 patients in the posterior group and 224 patients in the anterior group. The median patient age was 1.3 months, and the most common etiologies of hydrocephalus were postintraventricular hemorrhage secondary to prematurity (32.7%), myelomeningocele (16.8%), and aqueductal stenosis (10.8%). There was no significant difference in the time to shunt failure between the entry sites (log-rank test, stratified by age < 6 months and ≥ 6 months; p = 0.061). The hazard ratio (HR) of a posterior shunt relative to an anterior shunt was calculated using a univariable Cox regression model and was nonsignificant (HR 1.35, 95% CI, 0.98–1.85; p = 0.062). No significant difference was found between entry sites for the surgery duration, number of ventricular catheter passes, ventricular catheter location, and hospital length of stay. There were no significant differences between entry sites for intraoperative complications, postoperative CSF leaks, pseudomeningoceles, shunt infections, skull fractures, postoperative seizures, new-onset epilepsy, or intracranial hemorrhages.

### CONCLUSIONS

This randomized controlled trial comparing the anterior and posterior shunt entry sites has demonstrated no significant difference in the time to shunt failure. Anterior and posterior entry site surgeries were found to have similar outcomes and similar complication rates.

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## Clinical profiles and outcomes of deep brain stimulation in G2019S LRRK2 Parkinson disease

### OBJECTIVE

The objective of this study was to evaluate clinical features and response to deep brain stimulation (DBS) in G2019S LRRK2-Parkinson disease (LRRK2-PD) and idiopathic PD (IPD).

### METHODS

The authors conducted a clinic-based cohort study of PD patients recruited from the Mount Sinai Beth Israel Genetics database of PD studies. The cohort included 87 participants with LRRK2-PD (13 who underwent DBS) and 14 DBS participants with IPD enrolled between 2009 and 2017. The baseline clinical features, including motor ratings and levodopa-equivalent daily dose (LEDD), were compared among LRRK2-PD patients with and without DBS, between LRRK2-PD with DBS and IPD with DBS, and between LRRK2-PD with subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) DBS. Longitudinal motor scores (Unified Parkinson’s Disease Rating Scale–part III) and medication usage were also assessed pre- and postoperatively.

### RESULTS

Compared to LRRK2-PD without DBS (n = 74), the LRRK2-PD with DBS cohort (n = 13) had a significantly younger age of onset, longer disease duration, were more likely to have dyskinesia, and were less likely to experience hand tremor at disease onset. LRRK2-PD participants were also more likely to be referred for surgery because of severe dyskinesia (11/13 [85%] vs 6/14 [43%], p = 0.04) and were less likely to be referred for medically refractory tremor (0/13 [0%] vs 6/14 [43%], p = 0.02) than were IPD patients. Among LRRK2-PD patients, both STN-DBS and GPi-DBS targets were effective, although the sample size was small for both groups. There were no revisions or adverse effects reported in the GPi-DBS group, while 2 of the LRRK2-PD participants who underwent STN-DBS required revisions and a third reported depression as a stimulation-related side effect. Medication reduction favored the STN group.

### CONCLUSIONS

The LRRK2-PD cohort referred for DBS had a slightly different profile, including earlier age of onset and dyskinesia. Both the STN and GPi DBS targets were effective in symptom suppression. Patients with G2019S LRRK2 PD were well-suited for DBS therapy and had favorable motor outcomes regardless of the DBS target. LRRK2-DBS patients had longer disease durations and tended to have more dyskinesia. Dyskinesia commonly served as the trigger for DBS surgical candidacy. Medication-refractory tremor was not a common indication for surgery in the LRRK2 cohort.

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## Connectivity-based thalamus parcellation and surgical targeting of somatosensory subnuclei

### OBJECTIVE

The anatomy of the posterolateral thalamus varies substantially between individuals, presenting a challenge for surgical targeting. Patient-specific, connectivity-based parcellation of the thalamus may effectively approximate the ventrocaudal nucleus (Vc). This remains to be robustly validated or assessed as a method to guide surgical targeting. The authors assessed the validity of connectivity-based parcellation for targeting the Vc and its potential for improving clinical outcomes of pain surgery.

### METHODS

A cohort of 19 patients with regional, chronic neuropathic pain underwent preoperative structural and diffusion MRI, then progressed to deep brain stimulation targeting the Vc based on traditional atlas coordinates. Surgical thalami were retrospectively segmented and then parcellated based on tractography estimates of thalamocortical connectivity. The location of each patient’s electrode array was analyzed with respect to their primary somatosensory cortex (S1) parcel and compared across patients with reference to the thalamic homunculus.

### RESULTS

Ten patients achieved long-term pain relief. Sixty-one percent of an average array (interquartile range 42%–74%) was located in the S1 parcel. In patients who achieved long-term benefit from surgery, array location in the individually generated S1 parcels was medial for face pain, centromedial for arm pain, and centrolateral for leg pain. Patients who did not benefit from surgery did not follow this pattern. Standard stereotactic coordinates of electrode locations diverged from this pattern.

### CONCLUSIONS

Connectivity-based parcellation of the thalamus appears to be a reliable method for segmenting the Vc. Identifying the Vc in this way, and targeting mediolaterally as appropriate for the region of pain, merits exploration in an effort to increase the yield of successful surgical procedures.

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## Effects of a transsphenoidal surgery quality improvement program on patient outcomes and hospital financial performance

### OBJECTIVE

A comprehensive quality improvement (QI) program aimed at all aspects of patient care after pituitary surgery was initiated at a single center. This initiative was guided by standard quality principles to improve patient outcomes and optimize healthcare value. The programmatic goal was to discharge most elective patients within 1 day after surgery, improve patient safety, and limit unplanned readmissions. The program is described, and its effect on patient outcomes and hospital financial performance over a 5-year period are investigated.

### METHODS

Details of the patient care pathway are presented. Foundational elements of the QI program include evidence-based care pathways (e.g., for hyponatremia and pain), an in-house research program designed to fortify care pathways, patient education, expectation setting, multidisciplinary team care, standard order sets, high-touch postdischarge care, outcomes auditing, and a patient navigator, among other elements. Length of stay (LOS), outcome variability, 30-day unplanned readmissions, and hospital financial performance were identified as surrogate endpoints for healthcare value for the surgical epoch. To assess the effect of these protocols, all patients undergoing elective transsphenoidal surgery for pituitary tumors and Rathke’s cleft cysts between January 2015 and December 2019 were reviewed.

### RESULTS

A total of 609 adult patients who underwent elective surgery by experienced pituitary surgeons were identified. Patient demographics, comorbidities, and payer mix did not change significantly over the study period (p ≥ 0.10). The mean LOS was significantly shorter in 2019 versus 2015 (1.6 ± 1.0 vs 2.9 ± 2.2 midnights, p < 0.001). The percentage of patients discharged after 1 midnight was significantly higher in 2019 versus 2015 (75.4% vs 15.6%, p < 0.001). The 30-day unplanned hospital readmission rate decreased to 2.8% in 2019 from 8.3% in 2015. Per-patient hospital profit increased 71.3% ($10,613 ±$19,321 in 2015; $18,180 ±$21,930 in 2019), and the contribution margin increased 42.3% ($18,925 ±$19,236 in 2015; $26,939 ±$22,057 in 2019), while costs increased by only 3.4% ($18,829 ±$6611 in 2015; $19,469 ±$4291 in 2019).

### CONCLUSIONS

After implementation of a comprehensive pituitary surgery QI program, patient outcomes significantly improved, outcome variability decreased, and hospital financial performance was enhanced. Future studies designed to evaluate disease remission, patient satisfaction, and how the surgeon learning curve may synergize with other quality efforts may provide additional context.

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## Functional outcomes after resection of middle frontal gyrus diffuse gliomas

### OBJECTIVE

The clinical outcomes for patients undergoing resection of diffuse glioma within the middle frontal gyrus (MFG) are understudied. Anatomically, the MFG is richly interconnected to known language areas, and nearby subcortical fibers are at risk during resection. The goal of this study was to determine the functional outcomes and intraoperative mapping results related to resection of MFG gliomas. Additionally, the study aimed to evaluate if subcortical tract disruption on imaging correlated with functional outcomes.

### METHODS

The authors performed a retrospective review of 39 patients with WHO grade II–IV diffuse gliomas restricted to only the MFG and underlying subcortical region that were treated with resection and had no prior treatment. Intraoperative mapping results and postoperative neurological deficits by discharge and 90 days were assessed. Diffusion tensor imaging (DTI) tractography was used to assess subcortical tract integrity on pre- and postoperative imaging.

### RESULTS

The mean age of the cohort was 37.9 years at surgery, and the median follow-up was 5.1 years. The mean extent of resection was 98.9% for the cohort. Of the 39 tumors, 24 were left sided (61.5%). Thirty-six patients (92.3%) underwent intraoperative mapping, with 59% of patients undergoing an awake craniotomy. No patients had positive cortical mapping sites overlying the tumor, and 12 patients (33.3%) had positive subcortical stimulation sites. By discharge, 8 patients had language dysfunction, and 5 patients had mild weakness. By 90 days, 2 patients (5.1%) had persistent mild hand weakness only. There were no persistent language deficits by 90 days. On univariate analysis, preoperative tumor size (p = 0.0001), positive subcortical mapping (p = 0.03), preoperative tumor invasion of neighboring subcortical tracts on DTI tractography (p = 0.0003), and resection cavity interruption of subcortical tracts on DTI tractography (p < 0.0001) were associated with an increased risk of having a postoperative deficit by discharge. There were no instances of complete subcortical tract transections in the cohort.

### CONCLUSIONS

MFG diffuse gliomas may undergo extensive resection with minimal risk for long-term morbidity. Partial subcortical tract interruption may lead to transient but not permanent deficits. Subcortical mapping is essential to reduce permanent morbidity during resection of MFG tumors by avoiding complete transection of critical subcortical tracts.

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## Glibenclamide in aneurysmal subarachnoid hemorrhage: a randomized controlled clinical trial

### OBJECTIVE

Glibenclamide has been shown to improve outcomes in cerebral ischemia, traumatic brain injury, and subarachnoid hemorrhage (SAH). The authors sought to evaluate glibenclamide’s impact on mortality and functional outcomes of patients with aneurysmal SAH (aSAH).

### METHODS

Patients with radiologically confirmed aSAH, aged 18 to 70 years, who presented to the hospital within 96 hours of ictus were randomly allocated to receive 5 mg of oral glibenclamide for 21 days or placebo, in a modified intention-to-treat analysis. Outcomes were mortality and functional status at discharge and 6 months, evaluated using the modified Rankin Scale (mRS).

### RESULTS

A total of 78 patients were randomized and allocated to glibenclamide (n = 38) or placebo (n = 40). Baseline characteristics were similar between groups. The mean patient age was 53.1 years, and the majority of patients were female (75.6%). The median Hunt and Hess, World Federation of Neurosurgical Societies (WFNS), and modified Fisher scale (mFS) scores were 3 (IQR 2–4), 3 (IQR 3–4), and 3 (IQR 1–4), respectively. Glibenclamide did not improve the functional outcome (mRS) after 6 months (ordinal analysis, unadjusted common OR 0.66 [95% CI 0.29–1.48], adjusted common OR 1.25 [95% CI 0.46–3.37]). Similar results were found for analyses considering the dichotomized 6-month mRS score (favorable score 0–2), as well as for the secondary outcomes of discharge mRS score (either ordinal or dichotomized), mortality, and delayed cerebral ischemia. Hypoglycemia was more frequently observed in the glibenclamide group (5.3%).

### CONCLUSIONS

In this study, glibenclamide was not associated with better functional outcomes after aSAH. Mortality and delayed cerebral ischemia rates were also similar compared with placebo.

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

### OBJECTIVE

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

### METHODS

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

### RESULTS

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

### CONCLUSIONS

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

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## Letter to the Editor. Patient complaints

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