Despite the high incidence and burden of stroke, biological biomarkers are not used routinely in clinical practice to diagnose, determine progression, or prognosticate outcomes of acute ischemic ...stroke (AIS). Because of its direct interface with neural tissue, cerebrospinal fluid (CSF) is a potentially valuable source for biomarker development. This systematic review was conducted using three databases. All trials investigating clinical and preclinical models for CSF biomarkers for AIS diagnosis, prognostication, and severity grading were included, yielding 22 human trials and five animal studies for analysis. In total, 21 biomarkers and other multiomic proteomic markers were identified. S100B, inflammatory markers (including tumor necrosis factor-alpha and interleukin 6), and free fatty acids were the most frequently studied biomarkers. The review showed that CSF is an effective medium for biomarker acquisition for AIS. Although CSF is not routinely clinically obtained, a potential benefit of CSF studies is identifying valuable biomarkers from the pathophysiologic microenvironment that ultimately inform optimization of targeted low-abundance assays from peripheral biofluid samples (e.g., plasma). Several important catabolic and anabolic markers can serve as effective measures of diagnosis, etiology identification, prognostication, and severity grading. Trials with large cohorts studying the efficacy of biomarkers in altering clinical management are still needed.
INTRODUCTION:
Dorsal intradural arteriovenous fistulas (DI-AVFs) represent 70% of all spinal vascular malformations and 80% of all spinal AVFs. Microsurgical clip occlusion is a durable treatment for ...DI-AVFs and includes pre- and postoperative digital subtraction angiography (DSA) as the standard practice. Intraoperative indocyanine green videoangiography (ICG-VA) has become a valuable intraoperative adjunct in these cases. Results with intraoperative ICG-VA have not been compared to postoperative DSA.
METHODS:
A multi-institutional database of vascular malformations was queried for all surgically managed cases of DI-AVFs. Patients with both intraoperative ICG-VA and postoperative DSA were included. Demographic, radiologic, intraoperative findings, and surgical outcomes data were obtained and retrospectively analyzed.
RESULTS:
Forty-five cases of DI-AVFs were identified. Patients had a mean age of 61.9 years old (range 26-85), including 32 males and 13 females. Except for one asymptomatic patient, all other patients presented with leg numbness and weakness, gait instability, bowel and/or bladder incontinence, back pain, paresthesias, paraplegia, upper extremity discoordination, erectile dysfunction, and/or general weakness. The majority of lesions were diagnosed in the thoracic spine (72%). All DI-AVFs were treated with interruption of the fistula with clip occlusion of the draining vein. Intraoperative ICG-VA confirmed complete obliteration in all patients. Postoperative spinal angiography was performed on 40 patients confirming complete obliteration in all patients. More patients had clinical improvement compared to their preoperative state than stayed the same (47.4% vs. 42.1%).
CONCLUSIONS:
ICG-VA is useful for both intraoperative identification of DI-AVFs and confirmation of complete microsurgical occlusion. Perfect correlation between intraoperative ICG-VA and postoperative DSA demonstrates the diagnostic power of the former. This finding suggests that postoperative DSA is not necessary when intraoperative ICG-VA confirms complete occlusion of the DI-AVF, which will spare patients the procedural risk and cost of this invasive procedure.
INTRODUCTION:
Many factors influence an author’s choice for journal submission, including the journal impact factor and publication speed. These bibliometric data points, amongst others, have not yet ...been assessed in neurosurgical research.
METHODS:
Eight neurosurgical journals were analyzed for original articles, collected via randomized sampling per issue per year from 2016-2020. Publication speed data was gathered from published articles. Journal Impact Factors were gathered using Clarivate Journal Citation Reports. Spearman’s correlation analysis was used to analyze the findings.
RESULTS:
A total of 1617 original articles and systematic reviews across 8 neurosurgical journals were reviewed. The mean (standard deviation; SD, range) time from submission to print publication (SP) in neurosurgery journals is 344 (190) days, while the submission to acceptance (SA) time is 130 (104) days, acceptance to online print (AO) time is 76 (61) days, and the online publication to print publication (OP) is 137 (114) days. Most articles were from authors from the United States (n = 833; 52%), with the second and third highest contributions coming from China (n = 100; 6%) and Japan (n = 83, 5%) respectively. The top three neurosurgical topics published were spine (n = 417; 26%), vascular (n = 316; 20%) and oncology (n = 275; 17%). There were significant correlations across all determinants of publication speed and journal Impact Factors (SP: r = 0.457, SA: r = 0.204, AO: 0.481, OP: 0.317, p < 0.001).
CONCLUSIONS:
Neurosurgical journal publication speeds vary between journals and are significantly correlated with the journal’s impact factor. The majority of neurosurgical research in the past five years has been focused in spine, vascular, and oncology fields and has originated from the United States. The information on individual journals could serve as a guide for publishing neurosurgeons to determine the appropriate journal for submission.
INTRODUCTION:
Intramedullary spinal arteriovenous malformations (SpiAVM) are complex lesions. Due to their rarity, reports of their management and outcomes are limited.
METHODS:
Our neurovascular ...database was reviewed SpiAVMs between January 1986 and December 2021. Demographic, clinical, radiographic, and outcome data were obtained. Eccentric SpiAVMs were defined as those with a significant portion presenting through the pia mater into the subarachnoid space, with large vessels coursing outside the parenchyma. Concentric SpiAVMs were defined as those embedded within the spinal cord parenchyma, not presenting to pia mater, and well circumscribed.
RESULTS:
Fifty-nine patients (mean SD age, 34 15 years; female sex, 34) were identified. Patients exhibited myelopathy (88%), including pain (51%), paresis (88%), sensory deficits (46%), and bowel and bladder dysfunction (46%). Twenty-seven patients (46%) presented with hemorrhage. Forty-nine percent of lesions were located in the cervical spine and 51% in the thoracic spine. Thirty-five lesions (59%) were previously embolized. Twenty-eight patients (51%) were classified as eccentric and 27 (49%) as concentric SpiAVMs. Postoperative outcomes were similar with no significant differences (improved, 8/18 44% vs. 9/17 53%; unchanged, 8/18 44% vs. 7/17 41%; worse, 2/18 11% vs. 1/17 6%). Retreatment rates were not significantly different between both subtypes (eccentric, 9/28 32%; concentric, 6/27 22%). Eccentric and concentric SpiAVMs were associated with similar rates of complete resection (eccentric, 14/26 54%, concentric, 18/26 69%). Of 55 classifiable lesions, 4 (7%) were determined to have a mixed phenotype, harboring characteristics of eccentric and concentric SpiAVMs.
CONCLUSIONS:
Intramedullary AVMs may cause significant symptoms. The eccentric and concentric subtypes have different angioarchitecture and outcomes. While complete resection is usually the preferred surgical objective, eccentric SpiAVMs are amenable to the pial resection that may achieve angiographic obliteration without complete resection.
In the authors' microsurgical experience, the trans-middle cerebellar peduncle (MCP) approach to the lateral and central pons has been the most common approach to brainstem cavernous malformations ...(BSCMs). This approach through a well-tolerated safe entry zone (SEZ) allows a wide vertical or posterior trajectory, reaching pontine lesions extending into the midbrain, medulla, and pontine tegmentum. Better understanding of the relationships among lesion location, surgical trajectory, and long-term clinical outcomes could determine areas of safe passage.
A single-surgeon cohort study of all primary trans-MCP BSCM resections was conducted from July 1, 2017, to June 30, 2021. Preoperative and postoperative MR images were independently reviewed by 3 investigators blinded to the intervention, using a standardized rubric to define BSCM regions of interest (ROIs) involved with a lesion or microsurgical tract. Statistical testing, including the chi-square test with the Bonferroni correction, logistic regression, and structural equation modeling, was performed to analyze relationships between ROIs and clinical outcomes.
Thirty-one patients underwent primary trans-MCP BSCM resection during the study period. The median age was 50 years (IQR 24-49 years); 19 (61%) patients were female, and 12 (39%) were male. Seven (23%) patients had familial cavernous malformation syndromes. The median follow-up was 9 months (range 6-37 months). At the last follow-up, composite neurological outcomes were favorable: 22 (71%) patients had 0 (n = 12, 39%) or 1 (n = 10, 32%) major persistent deficit, 5 patients (16%) had 2 deficits, 2 (7%) had 3 deficits, and 1 patient each (3%) had 4 or 6 deficits. Unfavorable composite outcomes were significantly associated with lesions (OR 7.14, p = 0.04) or surgical tracts (OR 12.18, p < 0.001) extending from the superior cerebellar peduncle (SCP) into the contralateral medial midbrain. The ipsilateral dorsal pons was the most frequently implicated ROI involving a surgical tract and the development of new postoperative deficits. This region involved the rhomboid pontine territory and transgression of the pontine tegmentum (OR 7.53, p < 0.001). Structural equation modeling supported medial midbrain and pontine tegmentum transgression as the primary drivers of morbidity.
Trans-MCP resection is a safe and effective treatment for BSCMs, including lesions with marked superior or inferior ipsilateral extension. Two trajectories are associated with increased neurological risk: first, a superomedial trajectory to lesions extending into the midbrain that transgresses the SCP, its decussation, or both; and second, a posteromedial trajectory to lesions extending into the pontine tegmentum. The corticospinal tract, SCP, and pontine tegmentum form an invisible triangle within the pontine white matter tolerant of transgression. When the surgeon works within this triangle, most deep pontine BSCMs, including large lesions, those with contralateral or posterior extension, and others extending into the midbrain and medulla, can be resected safely with the trans-MCP approach.
INTRODUCTION:
Intramedullary spinal cord cavernous malformations (SCCMs) account for a small proportion (5%) of CMs overall and of spinal vascular malformations. However, they are well reported in ...the literature, with over 700 cases as of 2020. To date, the occurrence of recurrent or residual SCCMs has not been assessed or discussed, nor have the technical nuances of resection related to this issue.
METHODS:
An institutional database of vascular malformations was queried for all surgically managed cases of intramedullary cavernous malformations. Demographic, radiologic, intraoperative findings, and surgical outcomes data were obtained and retrospectively analyzed. A systematic review was performed using three databases (PubMed, Ovid MEDLINE, and Scopus) to analyze all cases of spinal cavernous malformations in the literature, to augment a prior review.
RESULTS:
146 cases of SCCM surgeries were identified in the database, including 17 recurrent lesions. Recurrences occurred at various time points, from as few as 3 to 264 months following initial resection. At the postoperative exam, 10 patients had better outcome scores than preoperative scores, 1 of which was status post resection of a recurrent lesion. A total of 21 patients had worse outcome scores, 4 of which were status post resection of recurrent lesion.
CONCLUSION:
Intramedullary spinal cord cavernous malformations are rare findings but may cause significant symptoms. Resection of these lesions is technically challenging, akin to the resection of brainstem cavernous malformations. Care should be taken to avoid leaving residual lesion, as this can leave the patient vulnerable to future hemorrhagic events and neurological morbidity. Satisfactory results are still achievable even with secondary or tertiary resections.
The objective of this paper was to assess applications of the supratentorial-infraoccipital (STIO) approach for cerebrovascular neurosurgery.
The authors conducted a cohort study of all consecutive ...cases in which the STIO approach was used during the study period, December 1995 to January 2021, as well as a systematic review of the literature.
Twenty-five cerebrovascular cases were identified in which the STIO approach was used. Diagnoses included arteriovenous malformation (n = 15), cerebral cavernous malformation (n = 5), arteriovenous fistula (n = 4), and aneurysm (n = 1). The arteriovenous malformations consisted of Spetzler-Martin grade II (n = 3), grade III (n = 8), and grade IV (n = 4) lesions. Lesion locations included the occipital lobe (n = 15), followed by the tentorial dural (n = 4), temporal-occipital (n = 3), temporal (n = 1), thalamic (n = 1), and quadrigeminal cistern (n = 1) regions. Many patients (75%) experienced transient visual deficits attributable to retraction of the occipital lobe, all of which resolved. As of last follow-up (n = 12), modified Rankin Scale scores had improved for 6 patients and were unchanged for 6 patients compared with the preoperative baseline.
The STIO approach is a safe and effective skull base approach that provides a specialized access corridor for appropriately selected cerebrovascular lesions.
In specialized neurosurgical centers, open microsurgery is routinely performed for aneurysmal subarachnoid hemorrhage (aSAH).
To compare the cost of endovascular vs microsurgical treatment for aSAH ...at a single quaternary center.
All patients undergoing aSAH treatment from July 1, 2014, to July 31, 2019, were retrospectively reviewed. Patients were grouped based on primary treatment (microsurgery vs endovascular treatment). The primary outcome was the difference in total cost (including hospital, discharge facility, and all follow-up) using a propensity-adjusted analysis.
Of 384 patients treated for an aSAH, 234 (61%) were microsurgically treated and 150 (39%) were endovascularly treated. The mean cost of index hospitalization for these patients was marginally higher ($9504) for endovascularly treated patients ($103 980) than for microsurgically treated patients ($94 476) ( P = .047). For the subset of patients with follow-up data available, the mean total cost was $45 040 higher for endovascularly treated patients ($159 406, n = 59) than that for microsurgically treated patients ($114 366, n = 105) ( P < .001). After propensity scoring (adjusted for age, sex, comorbidities, Glasgow Coma Scale score, Hunt and Hess grade, Fisher grade, aneurysms, and type/size/location), linear regression analysis of patients with follow-up data available revealed that microsurgery was independently associated with healthcare costs that were $37 244 less than endovascular treatment costs ( P < .001). An itemized cost analysis suggested that this discrepancy was due to differences in the rates of aneurysm retreatment and long-term surveillance.
Microsurgical treatment for aSAH is associated with lower total healthcare costs than endovascular therapy. Aneurysm surveillance after endovascular treatments, retreatment, and device costs warrants attention in future studies.
Addressing traumatic brain injury (TBI) heterogeneity is increasingly recognized as essential for therapy translation given the long history of failed clinical trials. We evaluated differential ...effects of a promising treatment (glibenclamide) based on dose, TBI type (patient selection), and imaging endophenotype (outcome selection). Our goal to inform TBI precision medicine is contextually timely given ongoing phase 2/planned phase 3 trials of glibenclamide in brain contusion.
Blinded randomized controlled preclinical trial of glibenclamide on MRI endophenotypes in two established severe TBI models: controlled cortical impact (CCI, isolated brain contusion) and CCI+hemorrhagic shock (HS, clinically common second insult).
Preclinical laboratory.
Adult male C57BL/6J mice (n = 54).
Mice were randomized to naïve, CCI±HS with vehicle/low-dose (20 μg/kg)/high-dose glibenclamide (10 μg/mouse). Seven-day subcutaneous infusions (0.4 μg/hr) were continued.
Serial MRI (3 hr, 6 hr, 24 hr, and 7 d) measured hematoma and edema volumes, T2 relaxation (vasogenic edema), apparent diffusion coefficient (ADC, cellular/cytotoxic edema), and 7-day T1-post gadolinium values (blood-brain-barrier BBB integrity). Linear mixed models assessed temporal changes. Marked heterogeneity was observed between CCI versus CCI+HS in terms of different MRI edema endophenotypes generated (all p < 0.05). Glibenclamide had variable impact. High-dose glibenclamide reduced hematoma volume ~60% after CCI (p = 0.0001) and ~48% after CCI+HS (p = 4.1 × 10-6) versus vehicle. Antiedema benefits were primarily in CCI: high-dose glibenclamide normalized several MRI endophenotypes in ipsilateral cortex (all p < 0.05, hematoma volume, T2, ADC, and T1-post contrast). Acute effects (3 hr) were specific to hematoma (p = 0.001) and cytotoxic edema reduction (p = 0.0045). High-dose glibenclamide reduced hematoma volume after TBI with concomitant HS, but antiedema effects were not robust. Low-dose glibenclamide was not beneficial.
High-dose glibenclamide benefitted hematoma volume, vasogenic edema, cytotoxic edema, and BBB integrity after isolated brain contusion. Hematoma and cytotoxic edema effects were acute; longer treatment windows may be possible for vasogenic edema. Our findings provide new insights to inform interpretation of ongoing trials as well as precision design (dose, sample size estimation, patient selection, outcome selection, and Bayesian analysis) of future TBI trials of glibenclamide.
