Why are clinical trials of deep brain stimulation terminated? An analysis of clinicaltrials.gov.

Background: Although deep brain stimulation (DBS) has established uses for patients with movement disorders and epilepsy, it is under consideration for a wide range of neurologic and neuropsychiatric conditions. Objective: To review successful and unsuccessful DBS clinical trials and identify factors associated with early trial termination. Methods: The ClinicalTrials.gov database was screened for all studies related to DBS. Information regarding condition of interest, study aim, trial design, trial success, and, if applicable, reason for failure was collected. Trials were compared and logistic regression was utilized to identify independent factors associated with trial termination. Results: Of 325 identified trials, 79.7% were successful and 20.3% unsuccessful. Patient recruitment, sponsor decision, and device issues were the most cited reasons for termination. 242 trials (74.5%) were interventional with 78.1% successful. There was a statistically significant difference between successful and unsuccessful trials in number of funding sources (p = 0.0375). NIH funding was associated with successful trials while utilization of other funding sources (academic institutions and community organizations) was associated with unsuccessful trials. 83 trials (25.5%) were observational with 84.0% successful; there were no statistically significant differences between successful and unsuccessful observational trials. Conclusion: One in five clinical trials for DBS were found to be unsuccessful, most commonly due to patient recruitment difficulties. The source of funding was the only factor associated with trial success. As DBS research continues to grow, understanding the current state of clinical trials will help design successful future studies, thereby minimizing futile expenditures of time, cost, and patient engagement.

Intraoperative MRI: A Review of Applications Across Neurosurgical Specialties.

Intraoperative MRI (iMRI) made its debut to great fanfare in the mid-1990s. However, the enthusiasm for this technology with seemingly obvious benefits for neurosurgeons has waned. We review the benefits and utility of iMRI across the field of neurosurgery and present an overview of the evidence for iMRI for multiple neurosurgical disciplines: tumor, skull base, vascular, pediatric, functional, and spine. Publications on iMRI have steadily increased since 1996, plateauing with approximately 52 publications per year since 2011. Tumor surgery, especially glioma surgery, has the most evidence for the use of iMRI contributing more than 50% of all iMRI publications, with increased rates of gross total resection in both adults and children, providing a potential survival benefit. Across multiple neurosurgical disciplines, the ability to use a multitude of unique sequences (diffusion tract imaging, diffusion-weighted imaging, magnetic resonance angiography, blood oxygenation level-dependent) allows for specialization of imaging for various types of surgery. Generally, iMRI allows for consideration of anatomic changes and real-time feedback on surgical outcomes such as extent of resection and instrument (screw, lead, electrode) placement. However, implementation of iMRI is limited by cost and feasibility, including the need for installation, shielding, and compatible tools. Evidence for iMRI use varies greatly by specialty, with the most evidence for tumor, vascular, and pediatric neurosurgery. The benefits of real-time anatomic imaging, a lack of radiation, and evaluation of surgical outcomes are limited by the cost and difficulty of iMRI integration. Nonetheless, the ability to ensure patients are provided by a maximal yet safe treatment that specifically accounts for their own anatomy and highlights why iMRI is a valuable and underutilized tool across multiple neurosurgical subspecialties.

Long-term outcomes of surgical clipping of saccular middle cerebral artery aneurysms: a consecutive series of 92 patients.

Despite advances in endovascular treatment, microsurgical clipping of middle cerebral artery (MCA) aneurysms remains appropriate. We review the high occlusion rate and treatment durability seen with surgical clipping of MCA aneurysms. We retrospectively reviewed patients who underwent microsurgical clipping of saccular MCA aneurysms by a single surgeon. Outcomes included aneurysm occlusion rate and durability, modified Rankin scale (mRS), and postoperative neurological morbidities. Ninety-two patients with 92 saccular MCA aneurysms were included, 50% of which were ruptured aneurysms. The mean follow-up period was 59 months. Complete aneurysm occlusion was achieved in all except one patient (99%) with near-complete occlusion. MCA aneurysm clipping was durable, with only one patient (1%) requiring retreatment after 4 years due to regrowth. Of the cohort, 79.3% achieved mRS 0-2 at last follow-up, including all with unruptured aneurysms. Poor outcome at discharge was associated with age > 65 (p = .03), postoperative neurological morbidities (p = .006), and aneurysm rupture (p < .001). Older age remained the single correlate for poor long-term outcome (p = .04). For ruptured aneurysms, predictors of poor long-term outcome included hemiparesis on presentation (p = .017), clinical vasospasm requiring treatment (p = .026), and infarction related to vasospasm (p = .041). Older age (p = .046) and complex anatomy (p = .036) were predictors of new postoperative neurological morbidities in the unruptured group. MCA aneurysm clipping is safe, durable, and should be considered first-line treatment for patients with saccular MCA aneurysms, especially in centers with abundant surgical experience.

Pituitary metastases: a case series and scoping review.

PURPOSE: To understand the natural history and optimal treatment strategy for pituitary gland metastasis. METHODS: We performed both a retrospective chart review of patients treated at our institution and a scoping review of the topic. RESULTS: The retrospective review identified seven patients with an average age of 59.6 years. Primary histologies included breast cancer (4), melanoma (1), renal cell carcinoma (1), and sarcoma (1). Two patients had anterior pituitary endocrine dysfunction, one of whom was the only patient with visual symptoms. All patients were treated with radiosurgery and two also underwent surgical resection. Overall survival ranged from 6.5 to 117 months. Literature review identified 166 patients from 71 studies. The most common primary cancer was lung (27.7%), followed by breast (18.7%) and renal (14.5%) cancer. 107 presented with endocrine dysfunction, including 41 cases of diabetes insipidus and 55 cases of hypopituitarism. 110 presented with visual compromise. 107 patients received radiotherapy, 96 underwent surgical resection and 44 received systemic chemotherapy/immunotherapy. Surgery was significantly associated with an increased likelihood of vision improvement and a decreased likelihood of endocrine normalization. Radiographic regression predicted visual improvement. Median overall survival was 9.9 months (range: 0.2-96). CONCLUSIONS: This scoping review showed that both radiosurgery and surgical resection have been frequently used to treat pituitary metastases with good response. Vision improvement is more likely to happen following surgical resection, likely at the expense of endocrine dysfunction. Despite treatment and radiographic response, patient survival remains less than a year.

Extreme lateral infracondylar approach for internal jugular vein compression syndrome: A case series with preliminary clinical outcomes.

BACKGROUND AND OBJECTIVES: Internal jugular vein (IJV) stenosis is associated with several neurological disorders including idiopathic intracranial hypertension (IIH) and pulsatile tinnitus. In cases of extreme bony compression causing stenosis in the infracondylar region, surgical decompression might be necessary. We aim to examine the safety and efficacy of surgical IJV decompression. METHODS: We retrospectively reviewed patients who received surgical IJV decompression via the extreme lateral infracondylar (ELI) approach between July 2020 and February 2022. RESULTS: Fourteen patients with IJV stenosis were identified, all with persistent headache and/or tinnitus. Six patients were diagnosed with IIH, three of whom failed previous treatment. Of the eight remaining patients, two failed previous treatment. All underwent surgical IJV decompression via styloidectomy, release of soft tissue, and removal of the C1 transverse process (TP). Follow-up imaging showed significant improvement of IJV stenosis in eleven patients and mild improvement in three. Eight patients had significant improvement in their presenting symptoms, and three had partial improvement. Two patients received IJV stenting after a lack of initial improvement. Two patients experienced cranial nerve paresis, and one developed a superficial wound infection. CONCLUSION: The ELI approach for IJV decompression appears to be safe for patients who are not ideal endovascular candidates due to bony anatomy. Confirming long-term efficacy in relieving debilitating clinical symptoms requires longer follow-up and a larger patient cohort. Carefully selected patients with symptomatic bony IJV compression for whom there are no effective medical or endovascular options may benefit from surgical IJV decompression.

Topic Reviews in Neurosurgical Journals: An Analysis of Publication Trends.

BACKGROUND: Topic review articles have become increasingly popular, even as the neurosurgical community looks to peer-reviewed journals as a source of discovery in basic and clinical science. In this study we quantify the prevalence of topic review articles in top neurosurgery journals. METHODS: The top 20 neurosurgery journals were defined by Google Scholar metrics. The PubMed database quantified the number of topic reviews compared with the total number of articles published; data were analyzed for trends between 1945 and 2022. RESULTS: All 20 journals have published topic reviews since the start of records on PubMed. Total publications have increased from <500 before 1980 to >8000 in 2022. Topic reviews have increased from <1% before 1980, to 2% by 2000, and to 3%-4% since 2010. The linear trend line equation for the total percentage of reviews in all journals shows a small increase in topic reviews per year. Three journals decreased review publication whereas 4 have reached prevalence >10%. The prevalence of topic reviews increased significantly from the first (2.13) to the last (4.76) year of publication (P = 0.003). CONCLUSIONS: The increasing prevalence of topic reviews is seen in most neurosurgery journals, reflecting supply and demand. Although there are benefits to these articles, they do not contribute novel data. Actions such as defining and labeling this publication type in journals and databases will improve the transparency of research methods. Academic neurosurgeons should further expand their knowledge and not become focused only on introspection into and review of neurosurgical understanding and practice.

Exploring the Intersection of Artificial Intelligence and Neurosurgery: Let us be Cautious With ChatGPT.

BACKGROUND AND OBJECTIVES: ChatGPT is a novel natural language processing artificial intelligence (AI) module where users enter any question or command and receive a single text response within seconds. As AI becomes more accessible, patients may begin to use it as a resource for medical information and advice. This is the first study to assess the neurosurgical information that is provided by ChatGPT. METHODS: ChatGPT was accessed in January 2023, and prompts were created requesting treatment information for 40 common neurosurgical conditions. Quantitative characteristics were collected, and four independent reviewers evaluated the responses using the DISCERN tool. Prompts were compared against the American Association of Neurological Surgeons (AANS) "For Patients" webpages. RESULTS: ChatGPT returned text organized in paragraph and bullet-point lists. ChatGPT responses were shorter (mean 270.1 ± 41.9 words; AANS webpage 1634.5 ± 891.3 words) but more difficult to read (mean Flesch-Kincaid score 32.4 ± 6.7; AANS webpage 37.1 ± 7.0). ChatGPT output was found to be of "fair" quality (mean DISCERN score 44.2 ± 4.1) and significantly inferior to the "good" overall quality of the AANS patient website (57.7 ± 4.4). ChatGPT was poor in providing references/resources and describing treatment risks. ChatGPT provided 177 references, of which 68.9% were inaccurate and 33.9% were completely falsified. CONCLUSION: ChatGPT is an adaptive resource for neurosurgical information but has shortcomings that limit the quality of its responses, including poor readability, lack of references, and failure to fully describe treatment options. Hence, patients and providers should remain wary of the provided content. As ChatGPT or other AI search algorithms continue to improve, they may become a reliable alternative for medical information.

Direct-cortical visual evoked potential monitoring during brain tumor resection.

BACKGROUND: Visual evoked potential (VEP) recording is traditionally regarded as an unreliable evoked potential monitoring technique, precluding widespread use in intracranial neurosurgery. However, VEPs can serve as a useful intraoperative adjunct for real-time detection of mechanical damage to optic apparatuses. The low obtainability and prognostic utility of VEPs are associated with transcranial recording, which typically provides non-focal information and poor signal-to-noise ratio. Direct cortical VEP (DC-VEP) recordings may offer a solution. METHODS: We evaluated the obtainability of DC-VEPs as well as their prognostic utility in predicting postoperative visual function deterioration in a series of brain tumor patients undergoing craniotomies for tumor resection. Patient records were retrospectively reviewed for all consecutive patients undergoing brain tumor resections with DC-VEP monitoring. Pre- and postoperative visual fields were characterized from patient charts and associated with the presence of intraoperative monitoring alerts to determine the sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of DC-VEPs in detecting postoperative visual field deficits. RESULTS: Twenty-two patients (9 male, 13 female) were included, with a median age of 60 years. DC-VEPs were reliably detected in 19 of 23 included surgeries (82.6%). The reported sensitivity, specificity, PPV, and NPV in detecting postoperative visual field deficits was 60%, 92.9%, 75%, and 86.7%, respectively. There was a statistically significant association between monitoring alerts and the presence of visual field deterioration by Fischer's exact test (p = 0.0374). CONCLUSIONS: DC-VEPs can be reliably obtained and are useful for detecting mechanical injury to optic areas and tracts during tumor resection.

A comparison of endovascular coil systems for the treatment of small intracranial aneurysms.

BACKGROUND: Endovascular coiling of small, intracranial aneurysms remains controversial and difficult, despite advances in technology. METHODS: We retrospectively reviewed data for 62 small aneurysms (<3.99 mm) in 59 patients. Occlusion rates, complications rates, and coil packing densities were compared between subgroups based upon coil type and rupture status. RESULTS: Ruptured aneurysms predominated (67.7%). Aneurysms measured 2.99 ± 0.63 mm by 2.51 ± 0.61 mm with an aspect ratio of 1.21 ± 0.34 mm. Brands included Optima (Balt) (29%), MicroVention Hydrogel (24.2%), and Penumbra SMART (19.4%) coil systems. Average packing density was 34.3 ± 13.5 mm3. Occlusion rate was 100% in unruptured aneurysms; 84% utilized adjuvant devices. For ruptured aneurysms, complete occlusion or stable neck remnant was achieved in 88.6% while recanalization occurred in 11.4%. No rebleeding occurred. Average packing density (p = 0.919) and coil type (p = 0.056) did not impact occlusion. Aspect ratio was smaller in aneurysms with technical complications (p = 0.281), and aneurysm volume was significantly smaller in those with coil protrusion (p = 0.018). Complication rates did not differ between ruptured and unruptured aneurysms (22.6 vs. 15.8%, p = 0.308) or coil types (p = 0.830). CONCLUSION: Despite advances in embolization devices, coiling of small intracranial aneurysms is still scrutinized. High occlusion rates are achievable, especially in unruptured aneurysms, with coil type and packing density suggesting association with complete occlusion. Technical complications may be influenced by aneurysm geometry. Advances in endovascular technologies have revolutionized small aneurysm treatment, with this series demonstrating excellent aneurysm occlusion especially in unruptured aneurysms.

Brainstem Metastases Treated with Stereotactic Radiosurgery: Masked versus Framed Immobilization.

BACKGROUND: Patients with brainstem metastases (BSMs) have minimal surgical options due to high-risk anatomy. To review our efficacy treating BSM using Gamma Knife stereotactic radiosurgery (SRS), we compared results on the basis of the utilization of mask-fixation (MF) or frame-fixation (FF). METHODS: Data were retrospectively collected for 32 patients. Follow-up data for 49 lesions were analyzed for local control rate (LCR) and objective response rate (ORR). RESULTS: Primary cancers included lung, breast, and melanoma; most lesions were pontine. MF was used in 18 patients. Average tumor volume was 0.99 cm3 (0.005-13.3 cm3). Thirty-nine lesions were treated with single-fraction 16 Gy. Ten lesions were treated in 3-5 fractions with mean dose of 22.5 Gy. Mean follow-up was 14.2 months (1.2-48.2 months). One-year LCR was 94.7%. ORR at last follow-up did not differ between MF and FF (P = 0.81). Average reduction of lesion volume at 6 and 12 months did not differ between MF and FF (64% vs. 45%, P = 0.77; 70% vs. 77%, P = 0.78). Failure occurred in a pontine colorectal cancer metastasis mask-immobilized for treatment with 14 Gy. CONCLUSIONS: SRS for BSM achieved high LCR despite variability in tumor size and histology with no significant difference between MF and FF. Although trials have historically excluded patients with BSM, our data support SRS as a safe and efficacious treatment. This is the first study showing that MF provides equivalent, successful outcomes when compared with FF for patients with BSM.

Disappearance of a small unruptured intracranial aneurysm: A case report and brief literature review.

Disappearing intracranial aneurysms are rare and have not been extensively reported in the literature. They are often small or partially thrombosed and carry a significant risk of recurrence. We discuss a unique case of a 65-year-old woman who presented in 2006 with a subarachnoid hemorrhage and was found to have a ruptured posterior communicating artery and an unruptured P1 aneurysm. Follow-up angiography and imaging showed no changes in the size of a left P1 aneurysm for 11 years (2006-2017). However, in 2021, 15 years after initial presentation, no aneurysm was seen on magnetic resonance angiography, and subsequent digital subtraction angiography in 2022 showed almost complete disappearance of the unruptured P1 aneurysm. Literature review reveals only six reported cases during which a small, unruptured anterior circulation aneurysm disappeared, or regressed on follow-up imaging and no reported cases in the posterior circulation.

Strain-dependent sex differences in a long-term forced swim paradigm.

Women are twice as likely as men to suffer from trauma- and stressor-related disorders. The development of improved therapeutic interventions is contingent upon a more complete grasp of both the neural and behavioral dynamics of the stress response in females. The rodent forced swim test (FST) is a valuable animal model for exploring the neurobiological mechanisms responsible for selection of active and passive responses to inescapable stressors, but it is often neglected in 2-day FST studies is the dissociation of innate (Day 1) versus learned (Day 2) coping responses. Here, we used a modified, long-term (4-week) FST paradigm and immunohistological analysis to study the interactions of sex, strain, and housing arrangement on selection of active and passive coping strategies in Sprague Dawley (SD) and Long Evans (LE) rats. We observed significant strain × sex interactions in both forced swim sessions with respect to both passive (immobility) and active (climbing and headshakes) responses. In immobility measures, we observed stable sex differences in SD rats and a stable lack of sex differences in LE rats across tests. In addition, both SD and LE females displayed significantly more headshakes than males during Test 1 and more climbing in Test 2. Most notably, males, but not females, exhibited a cross-test increase in immobility, suggesting that males and females may engage different learning processes in a 2-day FST. These sex differences corresponded to c-fos expression in the medial prefrontal cortex (mPFC), indicating that the mPFC may contribute to sexually dimorphic behavior in the FST. (PsycINFO Database Record