The role of surgical management for prolactin-secreting tumors in the era of dopaminergic agonists: An international multicenter report.

OBJECTIVE: First-line prolactin-secreting tumor (PST) management typically involves treatment with dopamine agonists and the role of surgery remains to be further explored. We examined the international experience of 12 neurosurgical centers to assess the patient characteristics, safety profile, and effectiveness of surgery for PST management. METHODS: Patients surgically treated for PST from January 2017 through December 2020 were evaluated for surgical characteristics, outcomes, and safety. RESULTS: Among 272 patients identified (65.1% female), the mean age was 38.0 ± 14.3 years. Overall, 54.4% of PST were macroadenomas. Minor complications were seen in 39.3% of patients and major complications were in 4.4%. The most common major complications were epistaxis and worsened vision. Most minor complications involved electrolyte/sodium dysregulation. At 3-6 months, local control on imaging was achieved in 94.8% of cases and residual/recurrent tumor was seen in 19.3%. Reoperations were required for 2.9% of cases. On multivariate analysis, previous surgery was significantly predictive of intraoperative complications (6.14 OR, p < 0.01) and major complications (14.12 OR, p < 0.01). Previous pharmacotherapy (0.27 OR, p = 0.02) and cavernous sinus invasion (0.19 OR, p = 0.03) were significantly protective against early endocrinological cure. Knosp classification was highly predictive of residual tumor or PST recurrence on 6-month follow-up imaging (4.60 OR, p < 0.01). There was noted institutional variation in clinical factors and outcomes. CONCLUSION: Our results evaluate a modern, multicenter, global series of PST. These data can serve as a benchmark to compare with DA therapy and other surgical series. Further study and longer term outcomes could provide insight into how patients benefit from surgical treatment.

Crooke Cell Adenoma Confers Poorer Endocrinological Outcomes Compared with Corticotroph Adenoma: Results of a Multicenter, International Analysis.

BACKGROUND: Crooke cell adenomas (CCAs) are a rare, aggressive subset of secretory pituitary corticotroph adenomas (sCTAs) found in 5%-10% of patients with Cushing disease. Multiple studies support worse outcomes in CCAs but are limited by small sample size and single-institution databases. We compared outcomes in CCA and sCTA using a multicenter, international retrospective database of high-volume skull base centers. METHODS: Patients surgically treated for pituitary adenoma from January 2017 through December 2020 were included. RESULTS: Among 2826 patients from 12 international centers, 20 patients with CCA and 480 patients with sCTA were identified. No difference in baseline demographics, tumor characteristics, or postoperative complications was seen. Microsurgical approaches (60% CCA vs. 62.3% sCTA) were most common. Gross total resection was higher in CCA patients (100% vs. 83%, P = 0.05). Among patients with gross total resection according to intraoperative findings, fewer CCA patients had postoperative hormone normalization of pituitary function (50% vs. 77.8%, P < 0.01) and remission of hypersecretion by 3-6 months (75% vs. 84.3%, P < 0.01). This was the case despite CCA having better local control rates (100% vs. 96%, P < 0.01) and fewer patients with remnant on magnetic resonance imaging (0% vs. 7.2%, P < 0.01). A systematic literature review of 35 studies reporting on various treatment strategies reiterated the high rate of residual tumor, persistent hypercortisolism, and tumor-related mortality in CCA patients. CONCLUSIONS: This modern, multicenter series of patients with CCA reflects their poor prognosis and reduced postsurgical hormonal normalization. Further work is necessary to better understand the pathophysiology of CCA to devise more targeted treatment approaches.

Defining benchmark outcomes for transsphenoidal surgery of pituitary adenomas: a multicenter analysis.

IMPORTANCE: Benchmarks aid in improve outcomes for surgical procedures. However, best achievable results that have been validated internationally for transsphenoidal surgery (TS) are not available. OBJECTIVE: We aimed to establish standardized outcome benchmarks for TS of pituitary adenomas. DESIGN: A total of 2685 transsphenoidal tumor resections from 9 expert centers in 3 continents were analyzed. SETTING: Patients were risk stratified, and the median values of each center's outcomes were established. The benchmark was defined as the 75th percentile of all median values for a particular outcome. The postoperative benchmark outcomes included surgical factors, endocrinology-specific values, and neurology-specific values. RESULTS: Of 2685 patients, 1149 (42.8%) defined the low-risk benchmark cohort. Within these benchmark cases, 831 (72.3%) patients underwent microscopic TS, and 308 (26.8%) patients underwent endoscopic endonasal resection. Of all tumors, 799 (29.8%) cases invaded the cavernous sinus. The postoperative complication rate was 19.6% with mortality between 0.0% and 0.8%. Benchmark cutoffs were ≤2.9% for reoperation rate, ≤1.9% for cerebrospinal fluid leak requiring intervention, and ≤15.5% for transient diabetes insipidus. At 6 months, benchmark cutoffs were calculated as follows: readmission rate: ≤6.9%, new hypopituitarism ≤6.0%, and tumor remnant ≤19.2%. CONCLUSIONS: This analysis defines benchmark values for TS targeting morbidity and mortality and represents the best outcomes in the best patients in expert centers. These cutoffs can be used to assess different centers, patient populations, and novel surgical techniques. It should be noted that the benchmark values may influence each other and must be evaluated in their own context.

A Multicenter, Propensity Score-Matched Assessment of Endoscopic Versus Microscopic Approaches in the Management of Pituitary Adenomas.

BACKGROUND AND OBJECTIVES: There is considerable controversy as to which of the 2 operating modalities (microsurgical or endoscopic transnasal surgery) currently used to resect pituitary adenomas (PAs) is the safest and most effective intervention. We compared rates of clinical outcomes of patients with PAs who underwent resection by either microsurgical or endoscopic transnasal surgery. METHODS: To independently assess the outcomes of each modality type, we sought to isolate endoscopic and microscopic PA surgeries with a 1:1 tight-caliper (0.01) propensity score-matched analysis using a multicenter, neurosurgery-specific database. Surgeries were performed between 2017 and 2020, with data collected retrospectively from 12 international institutions on 4 continents. Matching was based on age, previous neurological deficit, American Society of Anesthesiologists (ASA) score, tumor functionality, tumor size, and Knosp score. Univariate and multivariate analyses were performed. RESULTS: Among a pool of 2826 patients, propensity score matching resulted in 600 patients from 9 surgery centers being analyzed. Multivariate analysis showed that microscopic surgery had a 1.91 odds ratio (OR) ( P = .03) of gross total resection (GTR) and shorter operative duration ( P < .01). However, microscopic surgery also had a 7.82 OR ( P < .01) for intensive care unit stay, 2.08 OR ( P < .01) for intraoperative cerebrospinal fluid (CSF) leak, 2.47 OR ( P = .02) for postoperative syndrome of inappropriate antidiuretic hormone secretion (SIADH), and was an independent predictor for longer postoperative stay (ß = 2.01, P < .01). Overall, no differences in postoperative complications or 3- to 6-month outcomes were seen by surgical approach. CONCLUSION: Our international, multicenter matched analysis suggests microscopic approaches for pituitary tumor resection may offer better GTR rates, albeit with increased intensive care unit stay, CSF leak, SIADH, and hospital utilization. Better prospective studies can further validate these findings as matching patients for outcome analysis remains challenging. These results may provide insight into surgical benchmarks at different centers, offer room for further registry studies, and identify best practices.

An H3F3A K27M-mutation in a sonic hedgehog medulloblastoma.

Medulloblastomas are malignant embryonal brain tumours that may harbour mutations in histone-modifying genes, while mutations in histone genes have not been detected to date. We here describe the first SHH medulloblastoma with H3 K27M mutation. This may have diagnostic implications as H3 K27M mutations are the hallmark of diffuse midline gliomas, H3 K27M mutant, WHO grade IV. Medulloblastomas arise in midline structures and thus must not be mistaken for DMG when using an antibody detecting the H3 K27M mutation.

Intracranial emergencies during pregnancy requiring urgent neurosurgical treatment.

OBJECTIVE: Despite contemporary diagnostic and therapeutic techniques intracranial emergencies in the obstetric setting pose still a major challenge for the clinicians. There are limited guidelines and differing ethical views. Multidisciplinary teams are needed to support the pregnant woman in a way that she can deliver a viable and healthy child. The aim of the present study was to scrutinize the management of intracranial emergencies during pregnancy which needed urgent neurosurgical treatment. PATIENTS AND METHODS: Data of all pregnant women who presented with newly diagnosed intracranial pathologies and neurological symptoms caused by these pathologies in an emergency setting were collected over a 10-year period (2008-2018). Patient characteristics including maternal age, gestational age, and preoperative work-up of both mother and fetus were recorded. Furthermore, the surgical treatment, mode of delivery, and neonatal and maternal outcomes were analysed. RESULTS: The mean maternal age was 32.7 years and most patients were in their third trimester. There was one twin pregnancy (total of 12 fetuses). Five out of eleven pregnant women suffered from intracerebral haemorrhage (epidural haematoma (1), arteriovenous malformation (1), subarachnoid haemorrhage (2) and intracerebral haemorrhage (1)) and the other six patients had intracranial neoplasms (primary meningeal sarcoma (1), trigeminal schwannoma (1), anaplastic astrocytoma (2), glioblastoma (1) and sphenoid wing meningioma (1)).Neurosurgical procedures were performed via craniotomies in eight patients. A stereotactic biopsy via a frontal burr hole was achieved one patient. The two other patients with subarachnoid haemorrhage due to rupture of PICA aneurysms were treated with coil embolization. Depending on the gestational age and the clinical condition of the pregnant women it was decided to perform an emergency Caesarean section prior to further therapeutic measures in seven patients. Two out of 12 fetuses were unviable. Six women survived, while five women succumbed to the intracranial pathology. CONCLUSION: The individualized treatment approach in this peculiar obstetric scenario needs to consider various issues such as the clinical condition of the pregnant woman, prognosis of the disease, gestational age and the status of the pregnancy. The primary concern in this context must be the mother`s health and safety. Caesarean section is the primary mode of delivery in most cases. While contemporary care can insure survival for the majority of infants, maternal mortality still poses an extraordinary challenge. Interdisciplinary consulting of the patient and/or her family is necessary to develop a treatment strategy for both the expectant woman and her offspring.

Severe Bilateral Kinetic Tremor Due to Unilateral Midbrain Lesions.

Background: The dentatothalamic tract connects the dentate nucleus of the cerebellum with the contralateral thalamus and plays a major role in the pathogenesis of tremor. Unilateral lesions of the dentatothalamic pathway may affect its ipsilateral predecussational or its contralateral postdecussational course, which results either in ipsilateral or in contralateral tremor. Case Report: Here, we present two patients with a unilateral midbrain lesion resulting in bilateral tremor. Both patients presented with severe kinetic tremor. Discussion: The corresponding unilateral mesencephalic lesion affected both the ipsilateral predecussational and the ipsilateral postdecussational dentatothalamic tract originating from the contralateral dentate nucleus, which is very unusual and has not been outlined clearly before.

Tarlov cysts: long-term follow-up after microsurgical inverted plication and sacroplasty.

PURPOSE: Surgical treatment of Tarlov cysts is still a matter of debate. Published literature thus far includes mainly small case series with retrospective evaluation and short-term follow-up. We present a novel microsurgical technique that combines the decompression of the nerve fibers with the prevention of recurrence. The long-term follow-up is provided. METHODS: The indication for surgery was incapacitating pain refractory to medical therapy for at least 6 months. The surgical technique consisted in microsurgical opening of the cyst, relief of CSF followed by secured inverted plication of the cyst wall, packing of remnant space with fat graft, and sacroplasty. Pain and neurological deficits were evaluated according to a modified Barrow National Institute score (BNI score, 0-5) and the Departmental Neuro Score (DNS score, 0-20). RESULTS: A total of 13 patients (9 women, 4 men) were operated and followed up to 14 years (mean FU 5.3 years). Mean age at surgery was 51.8 (±14) years. Pain and neurological deficits improved significantly in 11/13 patients (BNI score pre-OP 5 vs 3.1 ± 1.2 at 1-year-FU, and 2.8 ± 1.2 at last follow-up visit; DNS score pre-OP 5.5 ± 1.5 vs 2.8 ± 2.1 at 1-year follow-up, and 2.6 ± 2.2 at last follow-up visit. Two patients needed revision surgery due to reoccurrence of the cyst. One patient suffered deterioration of preexisting neurological deficit. CONCLUSIONS: The inverted plication technique combined with sacroplasty is a promising technique. It improves pain and neurological deficits on the long term in the majority of patients with symptomatic Tarlov cysts.

Mechanical stability analysis of reference clamp fixation in computer-assisted spine surgery.

BACKGROUND: Pedicle screw misplacement is a common complication, while 7% may result in neurological complications. Computer-assisted navigation improves the rate of ideally placed screws. Inappropriate reference marker attachment can cause major problems in the outcome and duration of surgery. OBJECTIVE: To improve fixation of reference bases by comparing different designs of spine clamps and measuring their stability against the relevant thoracic and lumbar anatomy. METHODS: Force needed to dislocate the clamp from the processus spinosus using defined fixation of 0.79, 0.90 and 1.02 Nm torque was evaluated. Force transmission from clamp to the processus spinosus was also examined. Artificial thoracic and lumbar vertebral bodies were used for attaching spine clamps of three different designs. An instrument transmitted linear force onto the reference clamp and recorded the force when dislocation occurred. Another device determined transmitted force for each clamp utilizing 0.79, 0.90, 1.02, 1.13 and 1.24 Nm torque. RESULTS: L-clamp had the most stable fixation in lumbar section for every torque and developed the greatest forces. These transmitted forces were similar to the less stable Y-design. I-design created the smallest forces and had the most stable fixation for thoracic spine. The Y- and the L-design caused a notably high number of fractures. CONCLUSION: Great force leads to great stability, but also creates more fractures, favoring the use of smaller forces. Specific anatomy adaptation is important. Different clamp designs create different forces, while still differing in stability depending on their application in the thoracic or the lumbar spine.

A customized modular reference array clamp for navigated spine surgery.

INTRODUCTION: The current authors have developed a modular system of reference array fixation which is tailored specifically to the spinal level being operated upon. They believe that this system may further increase the precision and accuracy of pedicle screw placement. MATERIALS AND METHODS: Two formalin-fixed whole body cadavers were used for this study. For cervical spine evaluation of the reference clamp, four odontoid screws (two per cadaver) for C1/C2-fusion and four lateral mass screws (two per cadaver) were implanted. Following navigated screw placement with 2D and 3D fluoroscopic verification, insertion of two lateral mass screws was performed. In the same way, lumbar and thoracic pedicle screws were implanted. Two pedicle screws were placed at two levels of the lumbar and two levels of the thoracic areas giving an overall of 16 screws implanted (8 cervical, 4 thoracic, and 4 lumbar). Postoperative evaluation involved comparison of postoperative 3D scans and preoperative planning images. A simple classification system was used for evaluation of any deviation from the planned trajectory. RESULTS: All pedicle screw placements were performed as planned without any technical problems. The reference array clamps remained in position at all the spinal levels at which they were employed with no loosening or displacement and no secondary damage to any of the spinous processes. Manual manipulation was performed but no displacement or slippage was observed. Image artefacts caused by the reference clamp were not significant as to obscure the area of interest. Both imaging modalities (Iso-C 3D and Vario 3D) generated sufficiently precise 3D images. There was no substantial difference in quality when those two systems were compared. DISCUSSION: Insufficient fixation of the reference clamp can lead to failure and complications. To date, no reference clamp systems have been developed specifically for navigated spine surgery. CONCLUSIONS: Stable reference array fixation is a critical step in navigated surgery. To date, the same reference clamps have been applied to the spinal anatomy as have been developed originally for the appendicular skeleton. The current investigators have developed a novel modular clamp and have demonstrated its efficacy in a cadaveric model.