Effect of neurosurgical residency programs on neurosurgical patient outcomes in a single health care system: a cohort study.

BACKGROUND: The evidence on the benefits and drawbacks of involving neurosurgical residents in the care of patients who undergo neurosurgical procedures is heterogeneous. We assessed the effect of neurosurgical residency programs on the outcomes of such patients in a large single-payer public health care system. METHODS: Ten population-based cohorts of adult patients in Ontario who received neurosurgical care from 2013 to 2017 were identified on the basis of procedural codes, and the cohorts were followed in administrative health data sources. Patient outcomes by the status of the treating hospital (with or without a neurosurgical residency program) within each cohort were compared with models adjusted for a priori confounders and with adjusted multilevel models (MLMs) to also account for hospital-level factors. RESULTS: A total of 46 608 neurosurgical procedures were included. Operative time was 8%-30% longer in hospitals with neurosurgical residency programs in 9 out of 10 cohorts. Thirty-day mortality was lower in hospitals with neurosurgical residency programs for aneurysm repair (odds ratio [OR] 0.30, 95% confidence interval [CI] 0.20-0.44), cerebrospinal fluid shunting (OR 0.52, 95% CI 0.34-0.79), intracerebral hemorrhage evacuation (OR 0.66, 95% CI 0.52-0.84), and posterior lumbar decompression (OR 0.32, 95% CI 0.15-0.65) in adjusted models. The mortality rates remained significantly different only for aneurysm repair (OR 0.19, 95% CI 0.05-0.69) and cerebrospinal shunting (OR 0.42, 95% CI 0.21-0.85) in MLMs. Length of stay was mostly shorter in hospitals with neurosurgical residents, but this finding did not persist in MLMs. Thirty-day reoperation rates did not differ between hospital types in MLMs. For 30-day readmission rates, only extracerebral hematoma decompression was significant in MLMs (OR 1.41, 95% CI 1.07-1.87). CONCLUSION: Hospitals with neurosurgical residents had longer operative times with similar to better outcomes. Most, but not all, of the differences between hospitals with and without residency programs were explained by hospital-level variables rather than direct effects of residents.

From amaurotic idiocy to biochemically defined lipid storage diseases: the first identification of GM1-Gangliosidosis.

On February 23rd 1936, a boy-child ("Kn") died in an asylum near Munich after years of severe congenital disease, which had profoundly impaired his development leading to inability to walk, talk and see as well as to severe epilepsy. While a diagnosis of "Little's disease" was made during life, his postmortem brain investigation at Munich neuropathology ("Deutsche Forschungsanstalt für Psychiatrie") revealed the diagnosis of "amaurotic idiocy" (AI). AI, as exemplified by Tay-Sachs-Disease (TSD), back then was not yet understood as a specific inborn error of metabolism encompassing several disease entities. Many neuropathological studies were performed on AI, but the underlying processes could only be revealed by new scientific techniques such as biochemical analysis of nervous tissue, deciphering AI as nervous system lipid storage diseases, e.g. GM2-gangliosidosis. In 1963, Sandhoff & Jatzkewitz published an article on a "biochemically special form of AI" reporting striking differences when comparing their biochemical observations of hallmark features of TSD to tissue composition in a single case: the boy Kn. This was the first description of "GM1-Gangliosidosis", later understood as resulting from genetically determined deficiency in beta-galactosidase. Here we present illustrative materials from this historic patient, including selected diagnostic slides from the case "Kn" in virtual microscopy, original records and other illustrative material available. Finally, we present results from genetic analysis performed on archived tissue proving beta-galactosidase-gene mutation, verifying the 1963 interpretation as correct. This synopsis shall give a first-hand impression of this milestone finding in neuropathology. Original paper: On a biochemically special form of infantile amaurotic idiocy. Jatzkewitz H., Sandhoff K., Biochim. Biophys. Acta 1963; 70; 354-356. See supplement 1.

Surgical Management of Meningiomas Involving the Torcula, Transverse Sinus, and Jugular Bulb: A Technical Note and Review of the Literature.

Meningiomas that invade the confluens sinuum are rare and require extensive preoperative planning. Here, we describe the surgical and radio-oncological management of an aggressive large occipital meningioma invading the superior sagittal sinus, torcula, right and left transverse sinus down to the level of the jugular bulb in a 21-year-old female patient. Details of the surgical approach are presented to highlight the planned staged resection of this tumor at the level of the torcula to initially debulk the lesion while preserving venous outflow through the patent's sinus. Once the tumor fully occluded the confluens, a second-stage en bloc resection ensued. Postsurgical adjuvant radiation therapy was delivered via fractionated external beam therapy which has provided local control of the tumor since. This case is being discussed in the context of the pertinent literature to demonstrate the highly complex interdisciplinary and staged management of partially intravascular meningiomas involving the major venous sinuses.

Wrong-Level Spine Surgery: Introduction of a Protocol for Avoidance of This Complication.

Wrong-level spine surgery, in which an operation is performed at a vertebral level different from the intended one, is a rare but serious complication with wide-ranging medical and legal effects. Although many protocols have been developed to prevent such a serious unfavorable event, the problem has not yet been eliminated. Research into the effectiveness of strategies to prevent wrong-level spine surgery is lacking. Herein, we describe a case of 44-year-old woman presented with neck pain and bilateral upper extremity weakness and numbness. Magnetic resonance imaging showed C5/6 and C6/7 disc herniations with spinal cord compression. The patient underwent anterior cervical discectomy and fusion; however, at the conclusion of the surgery, intraoperative radiographs showed that it was accomplished at C4/5 and C5/6-one level above the intended level. On the basis of this case and similar ones, a new protocol was developed that included implementation of a Spine Level Safety Checklist to document the reference point, the landmark, and the level of exposure that is marked on the intraoperative radiograph. Since implementation of this protocol, the incidence of wrong-level spine surgery at the senior author's institution has decreased from 4/7000 to 0/11,200. Adoption of this protocol by other centers is thus recommended to reduce the incidence of such complication.

Surgical Morbidity in Relation to the Surgical Approach for Olfactory Groove Meningiomas-A Pooled Analysis of 1016 Patients and Proposal of a New Reporting System.

Background: There is currently no consensus in the field regarding whether a frontal or lateral approach is superior for microsurgical resection of olfactory groove meningiomas (OGM). Due to the lack of uniformity in classifying lesions and inherent differences in reporting outcomes after varying operative approaches, the best practice for approaching these lesions is yet to be determined. Objective: This study aimed to assess various surgical approaches undertaken for OGMs, investigate procedural aspects influencing the extent of resection, and analyze the respective complication rate associated with each approach. We performed a comprehensive literature review of presenting signs and symptoms in OGM patients, their surgical management, and the reported surgical outcomes. To address the lack of uniform data reporting across studies and to take more recent translational studies into account, we developed a new classification system for OGMs that can remedy the existing deficiencies in comparability of reporting. Methods: We conducted a PRISMA-guided literature search for surgical reports on OGMs published in the MRI era using broad search terms such as 'olfactory groove meningioma' and 'surgery', which yielded 20,672 results. After title screening and removal of duplicates, we assessed 871 studies on the specific surgical management of olfactory groove meningiomas. Following the application of exclusion criteria and abstract screening, a set of 27 studies was chosen for the final analysis of a pooled cohort of these reported patient outcomes. Results: The final twenty-seven studies included in our in-depth analysis identified a total of 1016 individual patients who underwent open microsurgical resection of OGMs. The approaches used included: pterional/unilateral, bifrontal with variations, and anterior interhemispheric approaches. Across all studies, gross total resection (Simpson Grades I or II) was achieved in 91.4% of cases, and subtotal resection (Grades III and IV) was reported in 8.6% of cases. A cumulative twenty-seven percent of surgical OGM patients sustained some form of complications. Minor issues accounted for 22.2% (CSF leak, seizures, infection, transient cranial nerve palsies, hydrocephalus), whereas major issues comprised 4.7% (hemorrhage, ischemic infarct, malignant cerebral edema). We then examined the correlation between these complications and the surgical approach chosen. Among pooled cohort of 426 patients who underwent unilateral approaches, 14% experienced minor complications, and 2.1% experienced major complications. For the mixed cohort of 410 patients who underwent bifrontal approaches, 24.6% experienced minor complications, and 7% experienced major complications. Conclusions: Unilateral approaches appear to have lower complication rates for the resection of OGMs compared to bilateral approaches. However, the extent of resection is not uniformly reported, making it difficult to identify differences. The use of an improved preoperative classification and scoring system can help establish a more coherent system to select the most suitable approach and to uniformly report surgical outcomes, such as EOR and complication rates specific to a given OGM and its surgical approach.

UBE3A and transsynaptic complex NRXN1-CBLN1-GluD1 in a hypothalamic VMHvl-arcuate feedback circuit regulates aggression.

The circuit origins of aggression in autism spectrum disorder remain undefined. Here we report Tac1-expressing glutamatergic neurons in ventrolateral division of ventromedial hypothalamus (VMHvl) drive intermale aggression. Aggression is increased due to increases of Ube3a gene dosage in the VMHvl neurons when modeling autism due to maternal 15q11-13 triplication. Targeted deletion of increased Ube3a copies in VMHvl reverses the elevated aggression adult mice. VMHvl neurons form excitatory synapses onto hypothalamic arcuate nucleus AgRP/NPY neurons through a NRXN1-CBLN1-GluD1 transsynaptic complex and UBE3A impairs this synapse by decreasing Cbln1 gene expression. Exciting AgRP/NPY arcuate neurons leads to feedback inhibition of VMHvl neurons and inhibits aggression. Asymptomatic increases of UBE3A synergize with a heterozygous deficiency of presynaptic Nrxn1 or postsynaptic Grid1 (both ASD genes) to increase aggression. Targeted deletions of Grid1 in arcuate AgRP neurons impairs the VMHvl to AgRP/NPY neuron excitatory synapses while increasing aggression. Chemogenetic/optogenetic activation of arcuate AgRP/NPY neurons inhibits VMHvl neurons and represses aggression. These data reveal that multiple autism genes converge to regulate the VMHvl-arcuate AgRP/NPY glutamatergic synapse. The hypothalamic circuitry implicated by these data suggest impaired excitation of AgRP/NPY feedback inhibitory neurons may explain the increased aggression behavior found in genetic forms of autism.

Traumatic brain injury in pregnancy: A systematic review of epidemiology, management, and outcome.

OBJECTIVE: Traumatic brain injury (TBI) during pregnancy is an extremely rare condition in our neurosurgical emergency practices. Studies on the epidemiology and management of TBI in pregnancy are limited to case reports or serial case reports. There is no specific guidelines of management of TBI in pregnancy yet. METHODS: The authors performed a structured search of all published articles on TBI in pregnancy from 1990 to 2020. We restricted search for papers in English and Bahasa. RESULTS: The literature search yielded 22 articles with total 43 patients. We distinguished C-section based on its timing according to the neurosurgical treatment into primary (simultaneous or prior to neurosurgery) and secondary group (delayed C-section). The mean GOS value in primary C-section is better compared to secondary C-section in severe TBI group (3.57 ± 1.47 vs 3.0 ± 1.27, respectively) consistently in the moderate TBI group (4.33 ± 1.11 vs 3.62 ± 1.47, respectively). The fetal death rate in primary C-section is lower compared to secondary C-section in severe TBI group (14.2 % vs 33.3 %, respectively), contrary, in moderate TBI group (16.7 % vs 12.5 %, respectively). CONCLUSIONS: Care of pregnant patients with TBI often requires multidisciplinary approach to optimize treatment strategy on a case-by-case basis in light of prior experience across different center. We propose management guideline for head injury in pregnancy.

Efficacy and Safety of Primary Stereotactic Radiosurgery in Patients With Intraventricular Meningiomas.

Purpose: Primary stereotactic radiosurgery for intraventricular meningiomas remains controversial owing to the potential for life-threatening peritumoral edema and lack of long-term follow-up data. We review the literature and present the largest series to assess efficacy and safety of primary stereotactic radiosurgery. Methods and Materials: A systematic review of the literature for primary stereotactic radiosurgery for intraventricular meningiomas was conducted. The retrospective series presented here comprised 33 patients who received primary stereotactic radiosurgery between 1999 and 2015 for a radiologically detected intraventricular meningioma. Demographic, diagnostic, and therapeutic data were extracted from medical records, imaging, and treatment-planning systems. Both standalone and pooled analysis were performed. Results: The mean patient age was 53 years, and 24 patients (73%) were female. The median Karnofsky performance status pretreatment was 80 (range, 60-100). The majority of lesions were located in the lateral ventricles (n = 32; 97%). The mean tumor volume was 8.7 cm3 (range, 0.6-44.55 cm3). The mean delivered dose was 1390.9 cGy. Complete imaging follow-up data were available for 21 patients (64%). Of those, 14 (67%) showed partial or marginal response, 7 (33%) had stable disease, and no patient progressed per Response Assessment in Neuro-Oncology criteria. On last follow-up, 32 patients (97%) had significant improvement in performance status and a decrease in pretreatment symptoms. No high-grade Common Terminology Criteria for Adverse Events (version 5.0) toxicity was observed with the dose range employed. Conclusions: Primary stereotactic radiosurgery for intraventricular meningiomas shows excellent treatment efficacy and low toxicity in patients with a long follow-up period. The best therapeutic algorithm remains to be established leveraging further clinical investigation.

The Emerging Applications of Nanotechnology in Neuroimaging: A Comprehensive Review.

Neuroimaging modalities such as computer tomography and magnetic resonance imaging have greatly improved in their ability to achieve higher spatial resolution of neurovascular and soft tissue neuroanatomy, allowing for increased accuracy in the diagnosis of neurological conditions. However, the use of conventional contrast agents that have short tissue retention time and associated renal toxicities, or expensive radioisotope tracers that are not widely available, continue to limit the sensitivity of these imaging modalities. Nanoparticles can potentially address these shortcomings by enhancing tissue retention and improving signal intensity in the brain and neural axis. In this review, we discuss the use of different types of nanotechnology to improve the detection, diagnosis, and treatment of a wide range of neurological diseases.

Tumor-Derived Cell Culture Model for the Investigation of Meningioma Biology.

Meningioma is the most common primary central nervous system tumor. Although mostly nonmalignant, meningioma can cause serious complications by mass effect and vasogenic edema. While surgery and radiation improve outcomes, not all cases can be treated due to eloquent location. Presently no medical treatment is available to slow meningioma growth owing to incomplete understanding of the underlying pathology, which in turn is due to the lack of high-fidelity tissue culture and animal models. We propose a simple and rapid method for the establishment of meningioma tumor-derived primary cultures. These cells can be maintained in culture for a limited time in serum-free media as spheres and form adherent cultures in the presence of 4% fetal calf serum. Many of the tissue samples show expression of the lineage marker PDG2S, which is typically retained in matched cultured cells, suggesting the presence of cells of arachnoid origin. Furthermore, nonarachnoid cells including vascular endothelial cells are also present in the cultures in addition to arachnoid cells, potentially providing a more accurate tumor cell microenvironment, and thus making the model more relevant for meningioma research and high-throughput drug screening.

Evaluation of Long-Term Outcomes and Toxicity After Stereotactic Phosphorus-32-Based Intracavitary Brachytherapy in Patients With Cystic Craniopharyngioma.

PURPOSE: Interstitial brachytherapy based on phosphorus-32 (P-32) has an established role as a minimally invasive treatment modality for patients with cystic craniopharyngioma. However, reporting on long-term outcomes with toxicity profiles for large cohorts is lacking in the literature. The purpose of this study is therefore to evaluate the long-term visual, endocrinal, and neurocognitive functions in what is the largest patient series having received this treatment to date. METHODS AND MATERIALS: We retrospectively evaluated 90 patients with cystic craniopharyngiomas who were treated with stereotactic intracavitary brachytherapy between 1998 and 2010. Colloidal activity of injected radioisotope P-32 was based on an even distribution within the tumor. After treatment, patients were followed-up for a minimum of 5 years and over a mean of 121 months (60-192 months) to assess radiographic and clinical responses. RESULTS: The 90 patients included in our study cohort underwent a total of 108 stereotactic surgical procedures for 129 craniopharyngioma-related cysts. Of the included tumors, 65 (72.2%) were associated with a single cyst, 15 (16.7%) were associated with 2 cysts, and 10 (11.1%) tumors had developed septations with 3 to 4 cysts. Stereotactic cyst puncture and content aspiration were used to drain a mean cyst fluid volume of 21.4 mL (1.0-55.0 mL). Each cyst was then instilled for interstitial brachytherapy with colloidal P-32 solution. Based on radiographic follow-up assessments, 56 cysts (43.4%) showed resolution and/or nonrecurrence, which was classified as a complete response to treatment; 47 cysts (36.4%) showed a partial response; and 5 cysts (3.9%) displayed a stable appearance. Treatment resulted in immediate and clinically significant vision improvement in 54 of 63 (86%) symptomatic patients, and this improvement was maintained. Progression-free survival rates at 5 and 10 years were 95.5% and 84.4%, respectively. CONCLUSIONS: P-32-based interstitial brachytherapy can play an effective role in managing patients with cystic craniopharyngiomas. It can be considered a valid alternative to surgery in select patients with a favorable toxicity profile and long-term clinical outcomes.

Pharmacoprophylaxis for Venous Thromboembolism in Spinal Surgery: A Systematic Review and Meta-analysis.

OBJECTIVE: Venous thromboembolism (VTE) is a significant contributor to postoperative morbidity and mortality. Prophylactic regimens for VTE involve mechanical prophylaxis and pharmacoprophylaxis. This systematic review and meta-analysis aimed to determine the efficacy and safety of pharmacoprophylaxis in comparison with any nonpharmacoprophylaxis regimen for the prevention of postoperative VTE in patients undergoing spinal surgery. METHODS: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and ICRCTN were searched for comparative studies including both pharmacoprophylaxis and nonpharmacoprophylaxis post spinal surgery. The primary outcome was the incidence of VTE within the postoperative hospitalized period. Secondary outcomes included the incidence of spinal epidural hematoma, significant bleeding events, and other adverse events associated with VTE. The data was pooled using random-effects models of meta-analysis and relative risk (RR) was calculated. RESULTS: Four retrospective and 3 randomized controlled trials representing a total of 8373 patients were included. Overall, there was a significant decrease in postoperative deep venous thrombosis with pharmacoprophylaxis versus nonpharmacoprophylaxis (RR 0.42, 95% confidence interval 0.21-0.86, P = 0.02, I2 = 0%); however, there were no significant differences between the groups in the incidences of VTE (RR 0.31, 95% confidence interval 0.12-0.81, P = 0.02, I2 = 0%). The incidences of spinal epidural hematoma and significant bleeding events were rare and comparable in both groups. CONCLUSIONS: This systematic review and meta-analysis found a potential benefit with pharmacoprophylaxis post spinal surgery in the prevention of deep venous thrombosis. However, there is a need for future randomized controlled trials to investigate the efficacy and safety of pharmacoprophylaxis in spinal surgery across various spinal procedures.

Relationship between pineal cyst size and aqueductal CSF flow measured by phase contrast MRI.

BACKGROUND: Most patients with pineal cysts referred for neurosurgical consultation have no specific symptoms or objective findings except for pineal cyst size to help in management decisions. Our purpose was to assess the relationship between pineal cyst size and aqueductal CSF flow using PC-MRI. METHODS: Eleven adult patients with pineal cysts (>1 cm) referred for neurosurgical consultations were included. Cyst volume was calculated using 3D T1 images. Phase contrast magnetic resonance imaging (PC-MRI) in axial plane with velocity encoding of 5 cm/sec was used to quantitatively assess CSF flow through the cerebral aqueduct to determine the aqueductal stroke volume, which was then correlated to cyst size using Pearson's correlation. Pineal cysts were grouped by size into small (6/11) and large (5/11) using the median value to compare aqueductal stroke volume using Mann-Whitney test. RESULTS: Patients were 39±13 years (mean±SD) of age, and 10/11 (91%) were female. There was significant negative correlation between cyst volume and aqueductal stroke volume (r=0.74; P=0.009). Volume of small cysts (4954±2157 mm3) was significantly different compared to large cysts (13,752±3738 mm3; P=0.008). The aqueductal stroke volume of patients harboring large cysts 33±8 µL/cardiac cycle was significantly lower than that of patients with small cysts 96±29 µL/cardiac cycle (P=0.008). CONCLUSIONS: Aqueductal CSF flow appears to decrease with increasing pineal cyst size. Our preliminary results provide first evidence that even in the absence of objective neurological findings or hydrocephalus; larger pineal cysts already display decreased CSF flow through the cerebral aqueduct.

Hemorrhagic Complications of Invasive Intracranial Pressure Monitor Placement in Acute Liver Failure: Outcomes of a Single-Center Protocol and Comprehensive Literature Review.

BACKGROUND: Elevated intracranial pressure due to cerebral edema is associated with very poor survival in patients with acute liver failure (ALF). Placing an intracranial pressure monitor (ICPm) aids in management of intracranial hypertension, but is associated with potentially fatal hemorrhagic complications related to the severe coagulopathy associated with ALF. METHODS: An institutional Acute Liver Failure Clinical Protocol (ALF-CP) was created to correct ALF coagulopathy prior to placing parenchymal ICP monitoring bolts. We aimed to investigate the frequency, severity, and clinical significance of hemorrhagic complications associated with ICPm bolt placement in the setting of an ALF-CP. All assessed patients were managed with the ALF-CP and had rigorous radiologic follow-up allowing assessment of the occurrence and chronology of hemorrhagic complications. We also aimed to compare our outcomes to other studies that were identified through a comprehensive review of the literature. RESULTS: Fourteen ALF patients were included in our analysis. There was no symptomatic hemorrhage after ICP monitor placement though four patients were found to have minor intraparenchymal asymptomatic hemorrhages after liver transplant when the ICP monitor had been removed, making the rate of radiographically identified clinically asymptomatic hemorrhage 28.6%. These results compare favorably to those found in a comprehensive review of the literature which revealed rates as high as 17.5% for symptomatic hemorrhages and 30.4% for asymptomatic hemorrhage. CONCLUSION: This study suggests that an intraparenchymal ICPm can be placed safely in tertiary referral centers which utilize a protocol such as the ALF-CP that aggressively corrects coagulopathy. The ALF-CP led to advantageous outcomes for ICPm placement with a 0% rate of symptomatic and low rate of asymptomatic hemorrhagic complications, which compares well to results reported in other series. A strict ICPm placement protocol in this setting facilitates management of ALF patients with cerebral edema during the wait time to transplantation or spontaneous recovery.