Risk factors and outcomes associated with external ventricular drain related hemorrhage.

OBJECTIVE: The objective of this study was to determine risk factors predictive of external ventricular drain (EVD)-related hemorrhage and the association of such hemorrhages with mortality, discharge disposition, length of stay (LOS), and total cost. METHODS: After Institutional Review Board approval, data was collected retrospectively for adult patients requiring EVD placement from 2015 to 2018 at the authors' institution. Collected data included demographic patient information, peri-procedural factors, and relevant post-procedural measures. Computerized tomography (CT) images and associated radiologic reports were independently reviewed, identifying hemorrhages accompanying EVD placement. RESULTS: From this 487-patient sample, 85 (17.5 %) patients had hemorrhages, including asymptomatic hemorrhages identified on imaging alone. A univariable analysis of patient parameters in the overall cohort was performed to identify possible predictors of hemorrhage. Age (p = 0.002), Charlson Comorbidity Index (CCI) (p < 0.001), platelet count (p = 0.002), presence of uremia (p = 0.035), and the number of times the EVD was replaced (p < 0.001) were associated with hemorrhage in univariable models. The experience of the resident surgeon based on post-graduate year (PGY level) and the number of attempts/passes needed for EVD placement were not associated with hemorrhage risk. Significant predictor of hemorrhage confirmed in a multivariable analysis only included the number of times the EVD was replaced (OR = 2.78, adjusted p < 0.001). Outcomes between EVD-related hemorrhage versus no hemorrhage groups, including mortality, discharge disposition, LOS, and cost, were compared. EVD-related hemorrhage was found to be associated with increased mortality (OR = 3.58, adjusted p < 0.001) and decreased likelihood of discharge home (OR = 0.13, adjusted p = 0.030) in the associated multivariable regressions. CONCLUSION: The number of times an EVD was replaced was associated with EVD-related hemorrhage outcome. EVD-related hemorrhage is associated with increased mortality and a decreased likelihood of being discharged home.

Active recharge biphasic stimulation for the intraoperative monopolar review in deep brain stimulation.

Introduction: Charge balancing is used in deep brain stimulation (DBS) to avoid net charge accumulation at the tissue-electrode interface that can result in neural damage. Charge balancing paradigms include passive recharge and active recharge. In passive recharge, each cathodic pulse is accompanied by a waiting period before the next stimulation, whereas active recharge uses energy to deliver symmetric anodic and cathodic stimulation pulses sequentially, producing a net zero charge. We sought to determine differences in stimulation induced side effect thresholds between active vs. passive recharge during the intraoperative monopolar review. Methods: Sixty-five consecutive patients undergoing DBS from 2021 to 2022 were retrospectively reviewed. Intraoperative monopolar review was performed with both active recharge and passive recharge for all included patients to determine side effect stimulation thresholds. Sixteen patients with 64 total DBS contacts met inclusion criteria for further analysis. Intraoperative monopolar review results were compared with the monopolar review from the first DBS programming visit. Results: The mean intraoperative active recharge stimulation threshold was 4.1 mA, while the mean intraoperative passive recharge stimulation threshold was 3.9 mA, though this difference was not statistically significant on t-test (p = 0.442). Mean stimulation threshold at clinic follow-up was 3.2 mA. In Pearson correlation, intraoperative passive recharge thresholds had stronger correlation with follow-up stimulation thresholds (Pearson r = 0.5281, p < 0.001) than intraoperative active recharge (Pearson r = 0.340, p = 0.018), however the difference between these correlations was not statistically significant on Fisher Z correlation test (p = 0.294). The mean difference between intraoperative passive recharge stimulation threshold and follow-up stimulation threshold was 0.8 mA, while the mean difference between intraoperative active recharge threshold and follow-up threshold was 1.2 mA. This difference was not statistically significant on a t-test (p = 0.134). Conclusions: Both intraoperative active recharge and passive recharge stimulation were well-correlated with the monopolar review at the first programming visit. No statistically significant differences were observed suggesting that either passive or active recharge may be utilized intraoperatively.

Neural Bypasses: Literature Review and Future Directions in Developing Artificial Neural Connections.

Reported neuro-modulation schemes in the literature are typically classified as closed-loop or open-loop. A novel group of recently developed neuro-modulation devices may be better described as a neural bypass, which attempts to transmit neural data from one location of the nervous system to another. The most common form of neural bypasses in the literature utilize EEG recordings of cortical information paired with functional electrical stimulation for effector muscle output, most commonly for assistive applications and rehabilitation in spinal cord injury or stroke. Other neural bypass locations that have also been described, or may soon be in development, include cortical-spinal bypasses, cortical-cortical bypasses, autonomic bypasses, peripheral-central bypasses, and inter-subject bypasses. The most common recording devices include EEG, ECoG, and microelectrode arrays, while stimulation devices include both invasive and noninvasive electrodes. Several devices are in development to improve the temporal and spatial resolution and biocompatibility for neuronal recording and stimulation. A major barrier to entry includes neuroplasticity and current decoding mechanisms that regularly require retraining. Neural bypasses are a unique class of neuro-modulation. Continued advancement of neural recording and stimulating devices with high spatial and temporal resolution, combined with decoding mechanisms uninhibited by neuroplasticity, can expand the therapeutic capability of neural bypassing. Overall, neural bypasses are a promising modality to improve the treatment of common neurologic disorders, including stroke, spinal cord injury, peripheral nerve injury, brain injury and more.

Microglia and Post-Subarachnoid Hemorrhage Vasospasm: Review of Emerging Mechanisms and Treatment Modalities.

Vasospasm is a potentially severe complication of subarachnoid hemorrhage. It can be attributed to neuroinflammation and the robust recruitment of microglia. Emerging evidence has linked this sustained inflammation to the development of delayed cerebral ischemia following subarachnoid hemorrhage. In this focused review, we provide an overview of the historical understanding of vasospasm. We then delve into the role of neuroinflammation and the activation of microglia. These activated microglia releases a host of inflammatory cytokines contributing to an influx of peripheral macrophages. This thereby opens a new and innovative treatment strategy to prevent vasospasm. Pre-clinical work has been promising, and the transition to clinical trials is warranted. Finally, some of the key mechanistic targets are outlined with emphasis on translation. This review will serve as a catalyst for researchers and clinicians alike in the quest to improve treatment options for vasospasm.

Patient satisfaction scores with telemedicine in the neurosurgical population.

BACKGROUND: The benefits of telemedicine in neurosurgery have been widely studied, especially as its implementation into clinical practice boomed at the start of the COVID-19 pandemic. However, few studies have investigated telemedicine from the perspective of the patient experience. OBJECTIVE: To evaluate patient satisfaction scores of telemedicine outpatient clinic visits in neurosurgery in comparison with in-person visits. METHODS: After obtaining Institutional Review Board approval, Press Ganey surveys from 3/1/2019 to 9/15/2020 were evaluated retrospectively from single-institution, academic neurosurgical clinics. Due to the non-normality of our data, stratified Wilcoxon tests were performed with correction for care provider differences. Domain score probability values were corrected for multiple comparisons. Average scores (range 20-100) are documented as mean ± standard deviation. RESULTS: The response rates were 20% (97 responders) for telemedicine visits and 19% (589 responders) for in-person visits. Patient overall satisfaction score was slightly higher with telemedicine visits compared to in-person corrected for care provider differences (94.2 ± 12.2 vs 93.1 ± 13.4, p = 0.085). The care provider domain demonstrated no statistically significant difference in telemedicine compared to in-person (94.7 ± 14.4 vs 92.4 ± 16.5, p = 0.096). The access domain (93.7 ± 12.3 vs 93.4 ± 12.4, p = 0.999) and overall domains (94.1 ± 12.1 vs 94.4 ± 13.4, p = 1.000) were not found to be different between visit types. CONCLUSION: Telemedicine appears to be a valuable option for neurosurgical patients and is not significantly different to in-person visits in all domains. This study demonstrates that telemedicine visits result in comparable satisfaction scores by neurosurgical patients, and providers should continue offering this option to their patients as we approach the post-COVID era.

Effect of Newer Generation Anticonvulsant Prophylaxis on Seizure Incidence After Spontaneous Intracerebral Hemorrhage.

BACKGROUND: The role of prophylactic antiepileptic drugs (AEDs) in preventing seizures and/or improving the outcomes after intracerebral hemorrhage (ICH) has remained controversial. The current guidelines have recommended against AED prophylaxis. However, these recommendations were based on older studies that had primarily used phenytoin as the AED of choice. Newer medications, such as levetiracetam, have yet to be extensively studied. METHODS: We performed a retrospective review of patients with ICH from 2010 to 2015. The patient demographic data, seizure data, and outcomes were collected. The results were analyzed using descriptive statistics, binary logistic regression, and quantile regression. The primary outcome was seizure incidence. RESULTS: A total of 360 patients with a median age of 70 years had met the inclusion criteria. Of the 360 patients, 30 (8.3%) had had recorded seizure events, 54% were men, and 81% had a history of hypertension. The median admission National Institutes of Health stroke scale (NIHSS) score was 7 (interquartile range [IQR], 14), and the median discharge NIHSS score was 5.0 (IQR, 13). The median hematoma size was 7.1 mL (IQR, 13 mL), and 143 patients (40%) had had cortical involvement. Of the 360 patients, 273 (76%) had received prophylaxis and 87 (24%) had not. After adjustment for the admission NIHSS and the presence of cortical involvement, the rate of new seizure events after ICH remained significantly lower for the patients who had received AED prophylaxis (adjusted odds ratio, 0.28; 95% confidence interval, 0.11-0.71; P = 0.008). CONCLUSION: The administration of, predominantly, levetiracetam for AED prophylaxis after ICH reduced the odds of new seizure events, independently of the admission NIHSS score and the presence of cortical involvement.

Frataxin levels in peripheral tissue in Friedreich ataxia.

OBJECTIVE: Friedreich ataxia (FRDA) is an autosomal recessive ataxia resulting from mutations in the frataxin gene (FXN). Such mutations, usually expanded guanine-adenine-adenine (GAA) repeats, give rise to decreased levels of frataxin protein in both affected and unaffected tissues. The goal was to understand the relationship of frataxin levels in peripheral tissues to disease status. METHODS: Frataxin levels were measured in buccal cells and blood, and analyzed in relation to disease features. Site-directed mutant frataxin was also transfected into human embryonic kidney cells to model results from specific point mutations. RESULTS: There was no evidence for change in frataxin levels over time with repeated measures analysis, although linear regression analysis of cross-sectional data predicted a small increase over decades. GAA repeat length predicted frataxin levels in both tissues, and frataxin levels themselves predicted neurological ratings (accounting for age). Compound heterozygous patients for a GAA expansion and a point mutation in FXN generally had lower levels of frataxin than those homozygous for the presence of two GAA repeat expansions, though levels varied dramatically between tissues in some compound heterozygotes for point mutations. The G130V mutation led to decreased levels of frataxin in vitro as well as in vivo, while the R165C mutation produced normal immunoreactive levels of frataxin both in vitro and in vivo. Start codon mutations led to low levels of frataxin in buccal cells but preserved immunoreactive frataxin levels in blood. INTERPRETATION: The present data show that peripheral frataxin levels reflect disease features in FRDA, but emphasize the need for interpretation of such levels in the context of specific mutations.

A vinylcyclobutane substrate designed as a cyclopropylcarbinyl radical probe.

Appending a spirocyclopropane linkage to bicyclo[3.2.0]hept-2-ene is achieved by selective kinetic cyclopropanation of 6-methylenebicyclo[3.2.0]hept-2-ene. The resultant vinylcyclobutane undergoes [1,3] migration as the dominant thermal process. A minor cyclopropylcarbinyl (CPC) rearrangement product clearly implicates a diradical transition structure. The presence and absence of other potential thermal products have enabled us to construct a detailed mechanistic proposal to account for all viable dynamic processes.