Faculty Bibliography

OBJECTIVE:Middle meningeal artery (MMA) embolization may be an effective means of inhibiting neovascularization of the subdural capsular membrane and preventing hematoma maintenance. We sought to better understand how the MMA may affect subdural hematoma physiology and how this process may be modified by embolization. METHODS:A retrospective review was done. We studied 27 patients with 29 SDHs who underwent MMA embolization from July 2018 to May 2019. Eight of these patients had post-embolization DynaCT imaging and were included. RESULTS:Average patient age was 75 years old. Baseline non-contrast head CT showed the presence of a hematoma membrane in all 8 patients. Post-embolization DynaCTs in all patients demonstrated enhancement of all four components (dura, capsular membrane, septations, and subdural hematoma fluid). All patients had a minimum 60-day imaging and clinical follow-up. There was an average 87% decrease in SDH volume at last follow-up compared to baseline. There was a significant difference between the average baseline and average last follow-up SDH volume (paired t-test, p < 0.0001) in all patients. Average last follow-up scan was 89 days (range 61-122 days) from the date of procedure. No patient experienced post-embolization complications, subsequent SDH drainage, or mortality. CONCLUSIONS:Our data lends support to the theory of contiguous vascular networks between the MMA and SDH membranes. Targeting these leaky vascular networks may remove the source of hematoma accumulation. This adds to the pathophysiological understanding of the disease and suggests potential insight into the mechanism of action of MMA embolization.

BACKGROUND AND PURPOSE/OBJECTIVE:Efficacy of restorative cognitive rehabilitation can be predicted from baseline patient factors. In addition, patient profiles of functional connectivity are associated with cognitive reserve and moderate the structure-cognition relationship in people with multiple sclerosis (PwMS). Such interactions may help predict which PwMS will benefit most from cognitive rehabilitation. Our objective was to determine whether patient response to restorative cognitive rehabilitation is predictable from baseline structural network disruption and whether this relationship is moderated by functional connectivity. METHODS:For this single-arm repeated measures study, we recruited 25 PwMS for a 12-week program. Following magnetic resonance imaging, participants were tested using the Symbol Digit Modalities Test (SDMT) pre- and postrehabilitation. Baseline patterns of structural and functional connectivity were characterized relative to healthy controls. RESULTS:= .385, P = .017, Interaction β = -.415). CONCLUSION/CONCLUSIONS:Patient response to restorative cognitive rehabilitation is predictable from the interaction between structural network disruption and functional connectivity in the default-mode network. This effect may be related to cognitive reserve.

INTRODUCTION:Embedded performance validity tests (PVTs) allow for continuous and economical validity assessment during neuropsychological evaluations; however, similar to their freestanding counterparts, a limitation of well-validated embedded PVTs is that the majority are memory-based. This study cross-validated several previously identified non-memory-based PVTs derived from language, processing speed, and executive functioning tests within a single mixed clinical neuropsychiatric sample with and without cognitive impairment. METHOD:This cross-sectional study included data from 124 clinical patients who underwent outpatient neuropsychological evaluation. Validity groups were determined by four independent criterion PVTs (failing ≤1 or ≥2), resulting in 98 valid (68% cognitively impaired) and 26 invalid performances. In total, 23 previously identified embedded PVTs derived from Verbal Fluency (VF), Trail Making Test (TMT), Stroop (SCWT), and Wisconsin Card Sorting Test (WCST) were examined. RESULTS:=.05-.22) with areas under the curve (AUCs) of.65-.81 and 19-54% sensitivity (≥89% specificity) at optimal cut-scores. When subdivided by impairment status, all PVTs except for WCST Failures to Maintain Set were significant (AUCs =.75-94) with 33-85% sensitivity (≥90% specificity) in the cognitively unimpaired group. Among the cognitively impaired group, most VF, TMT, and SCWT PVTs remained significant, albeit with decreased accuracy (AUCs =.65-.76) and sensitivities (19-54%) at optimal cut-scores, whereas all WCST PVTs were nonsignificant. Across groups, SCWT embedded PVTs evidenced the strongest psychometric properties. CONCLUSION:VF, TMT, and SCWT embedded PVTs generally demonstrated moderate accuracy for identifying invalid neuropsychological performance. However, performance on these non-memory-based PVTs from processing speed and executive functioning tests are not immune to the effects of cognitive impairment, such that alternate cut-scores (with reduced sensitivity if adequate specificity is maintained) are indicated in cases where the clinical history is consistent with cognitive impairment. In contrast, WCST indices generally had poor accuracy.

BACKGROUND AND PURPOSE/OBJECTIVE:Central retinal artery occlusion results in sudden, painless, usually permanent loss of vision in the affected eye. There is no proven, effective treatment to salvage visual acuity and a clear, unmet need for an effective therapy. In this work, we evaluated the efficacy of intravenous tissue-type plasminogen activator (IV alteplase) in a prospective cohort study and an updated systematic review and meta-analysis. METHODS:We enrolled consecutive patients with acute central retinal artery occlusion within 48 hours of symptoms onset and with a visual acuity of <20/200 from January 2009 until May 2019. The primary outcomes were safety and functional visual acuity recovery. We compared rates of visual recovery between those treated with alteplase within 4.5 hours of symptom onset to those who did not receive alteplase (including an analysis restricted to untreated patients presenting within the window for treatment). We incorporated these results into an updated systematic review and patient-level meta-analysis. RESULTS:=0.01). CONCLUSIONS:This study showed that the administration of intravenous alteplase within 4.5 hours of symptom onset is associated with a higher likelihood of a favorable visual outcome for acute central retinal artery occlusion. Our results strongly support proceeding to a randomized, placebo-controlled clinical trial.

BACKGROUND:Infection from the SARS-CoV-2 virus has led to the covid-19 pandemic. Given the large number of patients affected, healthcare personnel and facility resources are stretched to the limit; however, the need for urgent and emergent neurosurgical care continues. This article describes best practices when performing neurosurgical procedures on patients with covid-19 based on multi-institutional experiences. METHODS:We assembled neurosurgical practitioners from 13 different health systems from across the USA, including those in hot spots, to describe their practices in managing neurosurgical emergencies within the covid-19 environment. RESULTS:Patients presenting with neurosurgical emergencies should be considered as persons under investigation (PUI) and thus maximal personal protective equipment (PPE) should be donned during interaction and transfer. Intubations and extubations should be done with only anesthesia staff donning maximal PPE in a negative pressure environment. Operating room (OR) staff should enter the room once the air has been cleared of particulate matter. Certain OR suites should be designated as covid ORs, thus allowing for all neurosurgical cases on covid/PUI patients to be performed in these rooms, which will require a terminal clean post procedure. Each covid OR suite should be attached to an anteroom which is a negative pressure room with a HEPA filter, thus allowing for donning and doffing of PPE without risking contamination of clean areas. CONCLUSION/CONCLUSIONS:Based on a multi-institutional collaborative effort, we describe best practices when providing neurosurgical treatment for patients with covid-19 in order to optimize clinical care and minimize the exposure of patients and staff.

BACKGROUND:Headache mobile health (mHealth) applications (apps) have gained popularity in use but there is little research into what people with migraine find important to track. This information is important for helping with adherence and determining meaningful data to patients. We conducted several clinical trials using a headache research app (RELAXaHEAD). The app contains a "notes" feature (a free-text input section) where patients could record notes related to their headache. OBJECTIVE:To identify what patients view as important when tracking migraine/headaches within a headache tracking mHealth app. METHODS:This was a retrospective study where smartphone diary notes inputted by people with migraine were qualitatively analyzed; notes were extracted, a preliminary codebook was developed and used to code each note. Using grounded theory, themes and subthemes emerged. RESULTS:About 288 subjects in the trials used the notes function. There were 5364 total notes with an average of 18.6 ± 39.2 notes/user. The qualitative analysis yielded 759 unique codes and the emergence of 4 major themes. The first theme was "Utility in free-text tracking of headache characteristics, medications, and sleep" which emerged as a space for users to elaborate on data that could have been inputted into other sections of the app. The second theme was "Monitoring coexisting conditions both related to and distinct from headache." The third theme was "Personal records of behavioral therapy adherence," which included a range of concepts from behavioral therapy session frequency/adherence to subjects' thoughts or emotions regarding the behavioral therapy. The fourth theme was "Migraine trigger, prevention, and relief patterns deciphered through consistent data tracking." CONCLUSION/CONCLUSIONS:We found that the majority of patients choose to expand on information beyond what can be inputted into specific icons in a headache app. Moreover, they want to be able to monitor not only headache-related symptoms but symptoms they experience from other conditions. In addition to tracking their pharmacologic treatment, they may choose to track their nonpharmacologic, that is, behavioral therapy use, and they also use a smartphone diary app to assess what triggers versus relieves a migraine. While the RELAXaHEAD app was designed with features to extract data that would be useful to physicians and patients in treating migraine, our study results indicated that users also prefer a range of tracking capabilities that may or may not be useful to physicians but may be important for headache smartphone user engagement.

Cytokines were the first modern immunotherapies to produce durable responses in patients with advanced cancer, but they have only modest efficacy and limited tolerability^1,2. In an effort to identify alternative cytokine pathways for immunotherapy, we found that components of the interleukin-18 (IL-18) pathway are upregulated on tumour-infiltrating lymphocytes, suggesting that IL-18 therapy could enhance anti-tumour immunity. However, recombinant IL-18 previously did not demonstrate efficacy in clinical trials³. Here we show that IL-18BP, a high-affinity IL-18 decoy receptor, is frequently upregulated in diverse human and mouse tumours and limits the anti-tumour activity of IL-18 in mice. Using directed evolution, we engineered a 'decoy-resistant' IL-18 (DR-18) that maintains signalling potential but is impervious to inhibition by IL-18BP. Unlike wild-type IL-18, DR-18 exerted potent anti-tumour effects in mouse tumour models by promoting the development of poly-functional effector CD8⁺ T cells, decreasing the prevalence of exhausted CD8⁺ T cells that express the transcriptional regulator of exhaustion TOX, and expanding the pool of stem-like TCF1⁺ precursor CD8⁺ T cells. DR-18 also enhanced the activity and maturation of natural killer cells to effectively treat anti-PD-1 resistant tumours that have lost surface expression of major histocompatibility complex class I molecules. These results highlight the potential of the IL-18 pathway for immunotherapeutic intervention and implicate IL-18BP as a major therapeutic barrier.