Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Functional connectivity across the cortex has been posited to be important for consciousness and anesthesia, but functional connectivity patterns during the course of surgery and general anesthesia are unknown. The authors tested the hypothesis that disrupted cortical connectivity patterns would correlate with surgical anesthesia. Methods Surgical patients (n = 53) were recruited for study participation. Whole-scalp (16-channel) wireless electroencephalographic data were prospectively collected throughout the perioperative period. Functional connectivity was assessed using weighted phase lag index. During anesthetic maintenance, the temporal dynamics of connectivity states were characterized via Markov chain analysis, and state transition probabilities were quantified. Results Compared to baseline (weighted phase lag index, 0.163, ± 0.091), alpha frontal–parietal connectivity was not significantly different across the remaining anesthetic and perioperative epochs, ranging from 0.100 (± 0.041) to 0.218 (± 0.136) (P > 0.05 for all time periods). In contrast, there were significant increases in alpha prefrontal–frontal connectivity (peak = 0.201 [0.154, 0.248]; P < 0.001), theta prefrontal–frontal connectivity (peak = 0.137 [0.091, 0.182]; P < 0.001), and theta frontal–parietal connectivity (peak = 0.128 [0.084, 0.173]; P < 0.001) during anesthetic maintenance. Additionally, shifts occurred between states of high prefrontal–frontal connectivity (alpha, beta) with suppressed frontal–parietal connectivity, and high frontal–parietal connectivity (alpha, theta) with reduced prefrontal–frontal connectivity. These shifts occurred in a nonrandom manner (P < 0.05 compared to random transitions), suggesting structured transitions of connectivity during general anesthesia. Conclusions Functional connectivity patterns dynamically shift during surgery and general anesthesia but do so in a structured way. Thus, a single measure of functional connectivity will likely not be a reliable correlate of surgical anesthesia.
Concussion is a heterogeneous injury occurring throughout a range of impact magnitudes. Consequently, research focusing on a single or set of variables at the time of injury to understand concussive biomechanics has been thwarted by low injury prediction sensitivity. The current study examined the role of Impact Density in estimating concussive injury risk. Head impact data were collected across seven high school football seasons with the Head Impact Telemetry System (HIT System). Over the study period, 29 concussions were included for data analysis. The linear acceleration of the concussive impact was matched to a Control athlete, along with impacts in the 24 h before. Linear and rotational acceleration for the 19 impacts leading into the final event and the cumulative accelerations over time were evaluated. Analyses indicated no difference in impact counts within the final 24 h, or impact magnitudes for linear and rotational acceleration among the final 20 impacts (p > 0.05). A novel metric, Impact Density, was calculated from the final 20 impacts by summing the acceleration magnitude divided by time from the previous impact. Analyses indicated the Concussed athletes incurred a significantly higher linear (concussed: 255.4g/sec (standard error of the mean [SEM] = 40.1), controls:145.4g/sec (SEM = 23.8), p = 0.016), and rotational (Concussed:10311.3 rad/s/s/s (SEM = 1883.7), Controls: 6083.8 rad/s/s/s (SEM = 1115.9), p = 0.029) Impact Density than the Control athletes. Similar to other investigations, there was no difference in individual linear or rotational impact magnitude in the 20 impacts before and including the injury. The measure of Impact Density, however, revealed differences between the Concussed and Control athletes. These data suggest that the biomechanical threshold for concussion fluctuates downwardly with a greater impact magnitude and number with a return to pre-impact levels with time, suggesting physiological vulnerability to repeated head impacts. The current results highlight that time between impacts, not just impact magnitude, influences risk for concussion.
OBJECTIVE This prospective observational cohort study of high-school football athletes was performed to determine if high-acceleration head impacts (HHIs) that do not result in clinically diagnosed concussion still lead to increases in serum levels of biomarkers indicating traumatic brain injury (TBI) in asymptomatic athletes and to determine the longitudinal profile of these biomarkers over the course of the football season. METHODS Sixteen varsity high-school football athletes underwent baseline neurocognitive testing and blood sampling for the biomarkers tau, ubiquitin C-terminal hydrolase L1 (UCH-L1), neurofilament light protein (NF-L), glial fibrillary acidic protein (GFAP), and spectrin breakdown products (SBDPs). All athletes wore helmet-based accelerometers to measure and record head impact data during all practices and games. At various time points during the season, 6 of these athletes met the criteria for HHI (linear acceleration > 95 g and rotational acceleration > 3760 rad/sec ); in these athletes a second blood sample was drawn at the end of the athletic event during which the HHI occurred. Five athletes who did not meet the criteria for HHI underwent repeat blood sampling following the final game of the season. In a separate analysis, all athletes who did not receive a diagnosis of concussion during the season (n = 12) underwent repeat neurocognitive testing and blood sampling after the end of the season. RESULTS Total tau levels increased 492.6% ± 109.8% from baseline to postsession values in athletes who received an HHI, compared with 164% ± 35% in athletes who did not receive an HHI (p = 0.03). Similarly, UCH-L1 levels increased 738.2% ± 163.3% in athletes following an HHI, compared with 237.7% ± 71.9% in athletes in whom there was no HHI (p = 0.03). At the end of the season, researchers found that tau levels had increased 0.6 ± 0.2 pg/ml (p = 0.003) and UCH-L1 levels had increased 144.3 ± 56 pg/ml (p = 0.002). No significant elevations in serum NF-L, GFAP, or SBDPs were seen between baseline and end-of-athletic event or end-of-season sampling (for all, p> 0.05). CONCLUSIONS In this pilot study on asymptomatic football athletes, an HHI was associated with increased markers of neuronal (UCH-L1) and axonal (tau) injury when compared with values in control athletes. These same markers were also increased in nonconcussed athletes following the football season.
OBJECTIVEAcute low-pressure hydrocephalus (ALPH) is characterized by clinical manifestations of an apparent raised intracranial pressure (ICP) and ventriculomegaly despite measured ICP that is below the expected range (i.e., typically ≤ 5 cm H2O). ALPH is often refractory to standard hydrocephalus intervention protocols and the ICP paradox commonly leads to delayed diagnosis. The aim of this study was to characterize ALPH and develop an algorithm to facilitate diagnosis and management for patients with ALPH.METHODSEMBASE, MEDLINE, and Google Scholar databases were searched for ALPH cases from its first description in 1994 until 2019. Cases that met inclusion criteria were pooled with cases managed at the authors’ institution. Patient characteristics, presenting signs/symptoms, precipitating factors, temporizing interventions, definitive treatment, and patient outcomes were recorded.RESULTSThere were 195 patients identified, with 42 local and 153 from the literature review (53 pediatric patients and 142 adults). Decreased level of consciousness was the predominant clinical sign. The most common etiologies of hydrocephalus were neoplasm and hemorrhage. While the majority of ALPH occurred spontaneously, 39% of pediatric patients had previously undergone a lumbar puncture. Prior to ALPH diagnosis, 92% of pediatric and 39% of adult patients had a ventricular shunt in situ. The most common temporizing intervention was subatmospheric CSF drainage. The majority of patients underwent a shunt insertion/revision or endoscopic third ventriculostomy as definitive ALPH treatment. Although the mortality rate was 11%, 83% of pediatric and 49% of adult patients returned to their pre-ALPH neurological functional status after definitive treatment. Outcomes were related to both the severity of the underlying neurosurgical disease causing the hydrocephalus and the efficacy of ALPH treatment.CONCLUSIONSALPH is an underrecognized variant phenotype of hydrocephalus that is associated with multiple etiologies and can be challenging to treat as it frequently does not initially respond to standard strategies of CSF shunting. With early recognition, ALPH can be effectively managed. A management algorithm is provided as a guide for this purpose.
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