White matter tracts involved by deep brain stimulation of the subthalamic nucleus in Parkinson's disease: a connectivity study based on preoperative diffusion tensor imaging tractography.

Purpose: To depict the specific brain networks that are modulated by deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD), using diffusion tensor imaging-based fibre tractography (DTI-FT).Materials and methods: Nine patients who received bilateral STN-DBS for PD were included. Electrodes were localized by co-registering preoperative magnetic resonance imaging and postoperative computed tomography. The volume of tissue activated (VTA) was estimated as an isotropic, spherical electric field distribution centred at each effective electrode contact's centroid coordinates, taking into account individual stimulation parameters (i.e. voltage, impedance). Brain connectivity analysis was undertaken using a deterministic DTI-FT method, seeded from a single region of interest corresponding to the VTA. The labelling of the reconstructed white matter fibre tracts relied on their path and (sub)cortical termination territories.Results: Six months after surgery, we observed a statistically significant reduction in both the Unified Parkinson Disease Rating Scale part III and L-dopa equivalent daily dose. Areas consistently connected to the VTA included the brainstem (100%), cerebellum (94%), dorsal (i.e. supplementary motor area) and lateral premotor cortex (94%), and primary motor cortex (72%). An involvement of the hyperdirect pathway (HDP) connecting the STN and the (pre)motor cortex was demonstrated.Conclusions: The connectivity patterns observed in this study suggest that the therapeutic effects of STN-DBS are mediated through the modulation of distributed, large-scale motor networks. Specifically, the depiction of projection neurons connecting the stimulated area/STN to the (pre)motor cortex, reinforce the growing evidence that the HDP might be a potential therapeutic target in PD. If further replicated, these findings could raise the possibility that DTI-FT reconstruction of the HDP may critically improve DBS targeting and stimulation parameters selection, through the development of programming tools that incorporate VTA modelling and patient-specific DTI-FT data.

Assessing pain in the postoperative period: Analgesia Nociception IndexTMversus pupillometry.

BACKGROUND: Potential methods for objective assessment of postoperative pain include the Analgesia Nociception Index™ (ANI), a real-time index of the parasympathetic tone, the pupillary light reflex (PLR), and the variation coefficient of pupillary diameter (VCPD), a measure of pupillary diameter (PD) fluctuations. Until now, the literature is divided as to their respective accuracy magnitudes for assessing a patient's pain. The VCPD has been demonstrated to strongly correlate with pain in an obstetrical population. However, the pain induced by obstetrical labour is different, given its intermittent nature, than the pain observed during the postoperative period. The aim of the current study was to compare the respective values of these variables at VAS scores ≥4. METHODS: After approval by the Ethics Committee, 345 patients aged on average 50 (SD 17) yr (range: 18-91 yr) of age were included. The protocols of general anaesthesia and postoperative analgesia were left to the anaesthetist's discretion. Some 40 min after tracheal intubation, VAS, ANI, PD, PLR, and VCPD values were recorded. RESULTS: VCPD correlates more strongly (r=0.78) with pain as assessed with the VAS than ANI (r=-0.15). PD and PLR are not statistically correlated with VAS. The ability of VCPD to assess the pain of patients (VAS≥4) is strong [area under the curve (AUC): 0.92, confidence interval (CI): 0.89-0.95], and better than for ANI (AUC: 0.39, CI: 0.33-0.45). CONCLUSIONS: Our study suggests that VCPD could be a useful tool for monitoring pain in conscious patients during the postoperative period. CLINICAL TRIAL REGISTRATION: NCT03267979.

Autonomic cardiac regulation after general anesthesia in children.

BACKGROUND: General anesthesia dramatically decreases the activity of the autonomic nervous system. Most of the hypnotic agents used to induce anesthesia inhibit sympathetic cardiovascular regulation and baroreflex control in a dose-dependent manner, lowering cardiac adaptability during the operation. The consequence of this effect in children during and after surgery has never been studied to date. AIM: The aim of this study was to follow the variations in autonomic cardiac indices in children younger than 8 years old after general anesthesia (6-24 hours) in programmed surgery. METHOD: A prospective descriptive monocentric study of 44 children under 8 years old who underwent scheduled surgery at our hospital center (Saint-Étienne University Hospital, France) was performed between June 1, 2016 and November 1, 2016. Heart rate variability was monitored for 24 hours using Holter-ECG devices and the resulting data were interpreted using linear and nonlinear analyses. RESULTS: Compared to baseline thresholds before surgery, all heart rate variability indices decreased dramatically during general anesthesia. After awakening, a slight reduction in sympathetic activity persisted 6 hours after surgery, but all measurements of sympathetic and parasympathetic activity had returned to baseline thresholds 12 hours after the operation. Twenty-four hours after surgery, some parameters had increased above the corresponding baseline levels. CONCLUSION: Autonomic nervous function normalizes rapidly (within 12 hours) in prepubertal children. This study indicates that general anesthesia does not seem to increase the long-term risk of autonomic dysfunction in these patients.

Exploration of COVID-19 associated bradycardia using heart rate variability analysis in a case-control study of ARDS patients.

BACKGROUND: Bradycardia and dysautonomia observed during SARS-Cov2 infection suggests involvement of the autonomic nervous system (ANS). Limited data exists on ANS dysregulation and its association with outcomes in patients with acute respiratory distress syndrome (ARDS) related to COVID-19 (C-ARDS) or other etiologies (NC-ARDS). OBJECTIVES: We aimed to explore sympathovagal balance, assessed by heart rate variability (HRV), and its clinical prognostic value in C-ARDS compared with NC-ARDS. METHODS: A single-center, prospective case-control study was conducted. Consecutive patients meeting ARDS criteria between 2020 and 2022 were included. HRV was assessed using 1-hour electrographic tracing during a stable, daytime period. RESULTS: Twenty-four patients with C-ARDS and 19 with NC-ARDS were included. Age, sex and ARDS severity were similar between groups. The median heart rate was markedly lower in the C-ARDS group than in the NC-ARDS group (60 [53-72] versus 101 [91-112] bpm, p<.001). Most of HRV parameters were significantly increased in patients with C-ARDS. HRV correlated with heart rate only in patients with C-ARDS. A positive correlation was found between the low-to high-frequency ratio (LF/HF) and length of intensive care unit stay (r = 0.576, p<.001). CONCLUSION: This study confirmed that C-ARDS was associated with marked bradycardia and severe ANS impairment, suggesting a sympathovagal imbalance with vagal overtone. Poor outcomes appeared to be more related to sympathetic rather than parasympathetic hyperactivation.

Prognosis value of pupillometry in COVID-19 patients admitted in intensive care unit.

INTRODUCTION: ICU patients with SARS-CoV-2-related pneumonia are at risk to develop a central dysautonomia which can contribute to mortality and respiratory failure. The pupillary size and its reactivity to light are controlled by the autonomic nervous system. Pupillometry parameters (PP) allow to predict outcomes in various acute brain injuries. We aim at assessing the most predictive PP of in-hospital mortality and the need for invasive mechanical ventilation (IV). MATERIAL AND METHODS: We led a prospective, two centers, observational study. We recruited adult patients admitted to ICU for a severe SARS-CoV-2 related pneumonia between April and August 2020. The pupillometry was performed at admission including the measurement of baseline pupillary diameter (PD), PD variations (PDV), pupillary constriction velocity (PCV) and latency (PDL). RESULTS: Fifty patients, 90 % males, aged 66 (60-70) years were included. Seven (14 %) patients died in hospital. The baseline PD (4.1 mm [3.5; 4.8] vs 2.6 mm [2.4; 4.0], P = 0.009), PDV (33 % [27; 39] vs 25 % [15; 36], P = 0.03) and PCV (3.5 mm.s-1 [2.8; 4.4] vs 2.0 mm.s-1 [1.9; 3.8], P = 0.02) were significantly lower in patients who will die. A PD value <2.75 mm was the most predictive parameter of in-hospital mortality, with an AUC = 0.81, CI 95 % [0.63; 0.99]. Twenty-four (48 %) patients required IV. PD and PDV were significantly lower in patients who were intubated (3.5 mm [2.8; 4.4] vs 4.2 mm [3.9; 5.2], P = 0.03; 28 % [25; 36 %] vs 35 % [32; 40], P = 0.049, respectively). CONCLUSIONS: A reduced baseline PD is associated with bad outcomes in COVID-19 patients admitted in ICU. It is likely to reflect a brainstem autonomic dysfunction.

Comparison between pupillometry and numeric pain rating scale for pain assessments in communicating adult patients in the emergency department.

OBJECTIVE: The adequate assessment of pain in the emergency department (ED) can be challenging. Two dynamic pupillary measures used in conscious subjects after a surgical procedure were previously shown to correlate to the magnitude of ongoing pain. The objective of this study was to test the ability of dynamic measures derived from pupillometry to evaluate pain intensity in conscious adult patients admitted to the ED. METHODS: This prospective, interventional, single-centre study was performed between August 2021 and January 2022 (NCT05019898). An assessment of self-reported pain intensity was performed on ED admission by the triage nurse using a numeric rating scale (NRS). This was followed by two dynamic measures derived from pupillometry that were previously correlated with pain perception: the pupillary unrest under ambient light (PUAL) and the pupillary light reflex (PLR). RESULTS: Among the 313 analysed patients, the median age was 41 years, and 52% were women. No correlation was found between self-reported pain ratings and PUAL (r = 0.007) or PLR (baseline diameter r = -0.048; decrease r = 0.024; latency r = 0.019; slope = -0.051). Similarly, the pupillometry measures could not discriminate patients with moderate to severe pain (defined as NRS ≥4). CONCLUSIONS: Pupillometry does not appear to be an effective tool to evaluate pain in the ED environment. Indeed, too many factors influencing the sympathetic system-and thus the dynamic pupillary measures-are not controllable in the ED. SIGNIFICANCE: Pupillometry does not appear to be an effective tool to evaluate pain in the ED environment. There are several possible explanations for these negative results. The factors influencing the sympathetic system-and thus the PD fluctuations-are controllable in the postoperative period but not in the ED (e.g. full bladder, hypothermia). In addition, numerous psychological phenomena can impact pupillometry measurements such as emotional reactions or cognitive tasks. These phenomena are particularly difficult to control in the ED environment.

MFI-11 Predicts Post-Operative Serious Complications in Patients Undergoing Surgery for Odontoid Fractures.

STUDY DESIGN: Retrospective Cohort. OBJECTIVES: The objective of this study was to analyze postoperative complications in different mFI-11 groups after surgery for odontoid fractures in a geriatric population. METHODS: A single center retrospective review of odontoid fractures surgery (between 2013 and 2022) in patients aged 65 years and older was conducted. The primary outcome was the occurrence of a major complication (Calvien-Dindo ≥4) within 30 days post-surgery. The secondary outcome was the occurrence of a major complication within 3 months after surgery, and death within 1-month post-surgery. Survival curve, multi-variate analysis was performed and adjusted receiver operating characteristic curves were generated. RESULTS: There were 92 patients included in this study, with a mean age of 80.5 years. Serious complication occurred for 16 patients (17%) during hospitalization. Multivariate analysis demonstrated an mFI 11 >.27 was strongly and independently associated with serious complications within 1-month post-surgery (OR = 16.7, 95% CI = 4.50-83), as well as serious complications within 3 months post-surgery (OR = 11.8, 95% CI = 3.48-49.1) and death within 1 month post-surgery (OR = 11.7; 95% CI = 3.02-60.4). The Receiver Operator Characteristics (ROC) curves for the three models all have an Area Under the Curve (AUC) value greater than 0.7. CONCLUSIONS: The mFI-11 is a straightforward and validated tool that can be used during the preoperative period to identify the patient's level of frailty and assess their risk of postoperative complications. Patients with mFI-11 ≥.27 are at greater risk of serious complications within 1 and 3 months' post-surgery and death within 1 month post-surgery.

Sleep disturbances and related disordered breathing after hip replacement surgery: A randomised controlled trial.

INTRODUCTION: Mechanisms of postoperative sleep architecture disturbances and sleep-disordered breathing are uncertain. The authors hypothesised that patients undergoing surgery under regional anaesthesia without opioids used for postoperative analgesia would experience lesser changes in these parameters than patients operated under general anaesthesia with per- and postoperative opioids. PATIENTS AND METHODS: After ethical approval and informed consent, patients undergoing total hip replacement were included in a prospective, randomised trial comparing 3 groups of patients: (1) S-LPB group receiving spinal anaesthesia and postoperative analgesia by lumbar plexus block; (2) GA-PCA group receiving general anaesthesia and postoperative analgesia by morphine patient-controlled analgesia; (3) GA-LPB group receiving general anaesthesia and postoperative analgesia by lumbar plexus block. Outcome measurements were polysomnographic parameters of sleep architecture and sleep-disordered breathing. RESULTS: Eighteen patients completed the 5-night study protocol (preoperative night: N-1, postoperative nights: N1 to N4). The percentage of rapid eye movement (REM) sleep decreased by 49% and 47% during N1 in the GA-PCA and GA-LPB groups respectively. A rebound phenomenon of more than 40% in the GA-PCA group and 25% in the GA-LPB group was observed during N2 and N3. Apnoea hypopnoea index (AHI) and the number of arousals per hour were significantly increased during N2 and N3 when compared with N-1 in the GA-groups. No sleep architecture disturbances and no sleep-disordered breathing were measured in the S-LPB group. CONCLUSION: Postoperative sleep architecture and breathing pattern were disturbed in GA groups. Both were preserved under spinal anaesthesia associated with a free opioid postoperative analgesia.

Emotion Measurements Through the Touch of Materials Surfaces.

The emotion generated by the touch of materials is studied via a protocol based on blind assessment of various stimuli. The human emotional reaction felt toward a material is estimated through (i) explicit measurements, using a questionnaire collecting valence and intensity, and (ii) implicit measurements of the activity of the autonomic nervous system, via a pupillometry equipment. A panel of 25 university students (13 women, 12 men), aged from 18 to 27, tested blind twelve materials such as polymers, sandpapers, wood, velvet and fur, randomly ordered. After measuring the initial pupil diameter, taken as a reference, its variation during the tactile exploration was recorded. After each touch, the participants were asked to quantify the emotional value of the material. The results show that the pupil size variation follows the emotional intensity. It is significantly larger during the touch of materials considered as pleasant or unpleasant, than with the touch of neutral materials. Moreover, after a time period of about 0.5 s following the stimulus, the results reveal significant differences between pleasant and unpleasant stimuli, as well as differences according to gender, i.e., higher pupil dilatation of women than men. These results suggest (i) that the autonomic nervous system is initially sensitive to high arousing stimulation, and (ii) that, after a certain period, the pupil size changes according to the cognitive interest induced and the emotional regulation adopted. This research shows the interest of the emotional characterization of materials for product design.

Assessing Pain Using the Variation Coefficient of Pupillary Diameter.

Pupillary diameter (PD) varies under the influence of the sympathetic as well as parasympathetic systems, increasing proportionally with pain intensity. Such variations however, should not be confused with pupillary fluctuations, which refer to the fast and permanent PD fluctuations induced by the ongoing interplay between the sympathetic and parasympathetic systems, which we propose to measure using the variation coefficient of PD (VCPD). This study aimed first at correlating PD, PD increase during a contraction, and VCPD, with pain rated using a numeric rating scale (NRS) during obstetrical labor, and then at comparing such correlations with each other. Forty patients were included in the study, and 160 simultaneous ratings (NRS, PD, and VCPD) were taken: 40 in the presence of uterine contractions and 40 in the absence of such contractions, before and 20 minutes after epidural analgesia. VCPD correlates more strongly (r = .77) than PD increase (r = .42) with pain rated using a NRS. The ability of VCPD to predict the occurrence of NRS scores ≥4 during obstetrical labor is .97 (confidence interval, .93-1.0). When measured over 10 seconds during contraction, VCPD correlates more strongly than PD increase with pain rated using the NRS. Such stronger correlation allows for an easy assessment of antinociception-nociception balance. PERSPECTIVE: The VCPD allows for an objective assessment of pain in laboring women. It could allow for an easy assessment of pain in noncommunicating patients: newborns or very old patients, patients with serious psychological conditions, assessment during the immediate postoperative period, or in intensive care units.

Adrenal axis function does not appear to be associated with hemodynamic improvement in septic shock patients systematically receiving glucocorticoid therapy.

OBJECTIVE: There is mounting evidence showing the value of low-dose corticosteroids in patients with septic shock requiring vasopressor therapy. It remains unclear whether adrenal function tests should be carried out systematically to guide the decision on glucocorticoid therapy. METHODS: The retrospective study was conducted in 52 patients in three university hospital ICUs. We included consecutive patients with catecholamine-dependent septic shock who had not received ketoconazole, glucocorticoids, or etomidate in the 24 h before the ACTH test, and who had survived to day 3 after the shock onset. All patients had a 250-microg ACTH test before systematic glucocorticoid therapy was started. Various definitions of relative adrenal insufficiency were used (based on cortisol basal level and/or change in cortisol level after ACTH stimulation). We defined hemodynamic improvement as a 50% reduction in the vasoactive agent dose in the 3 days following the initiation of glucocorticoid treatment. The relationship between the hemodynamic improvement and the results of the adrenal function tests was analyzed. RESULTS: Hemodynamic improvement occurred in 29 patients (55.8%). Baseline characteristics, sites of infection, types of micro-organisms and antibiotic management did not differ between patients with and those without hemodynamic improvement. Relative adrenal insufficiency whatever the definition was not associated with hemodynamic improvement. CONCLUSION: In catecholamine-dependent septic shock patients managed with systematic glucocorticoid therapy the results of ACTH stimulation do not predict hemodynamic improvement.

Preoperative peribulbar block in patients undergoing retinal detachment surgery under general anesthesia: a randomized double-blind study.

Retinal detachment surgery is frequently associated with significant postoperative pain and emesis in adults. In this randomized, double-blind, controlled study we sought to demonstrate that 1% ropivacaine peribulbar (PB) block in conjunction with general anesthesia (GA) improves operative conditions and postoperative analgesia compared with GA combined with subcutaneous normal saline injection into the inferior eyelid. Thirty-one patients were included in each group. Anesthesia was performed with target-controlled infusion propofol and continuous remifentanil infusion adjusted to maintain bispectral index values between 40 and 50. Postoperative analgesia included fixed-dose IV infusion of propacetamol and IV injection of nefopam via a patient-controlled analgesia device. Tramadol was infused IV as rescue medication. Demographic data were comparable between the groups and bispectral index values were maintained at the objective target. In the PB group, fewer patients presented an oculocardiac reflex (6 versus 17; P < 0.01); bleeding interfering with the surgical field was reduced (1 versus 11 patients; P < 0.01); mean time to first nefopam request was longer (148 +/- 99 versus 46 +/- 58 min; P < 0.01); mean nefopam consumption was diminished during the first 6 h after tracheal extubation (18.9 +/- 13.9 versus 28.5 +/- 14.7 mg; P < 0.05); immediate postoperative pain scores were lower; and fewer patients required rescue medication (5 versus 23; P < 0.01). The two groups were similar with respect to the incidence of postoperative nausea and vomiting. Overall, PB block combined with GA improved operating conditions and postoperative analgesia in retinal detachment surgery.

Memantine plus vitamin D prevents axonal degeneration caused by lysed blood.

Intracranial hemorrhage, whether due to traumatic brain injury or ruptured cerebral aneurysm, is characterized by major neurological damage and a high mortality rate. Apart from cerebral vasospasm and mass effect, brain injury results from the release of unclotted blood that contacts neurons causing calcic stress. The combination of memantine with vitamin D, a neurosteroid hormone, may prevent blood neurotoxicity. Our purpose was to examine the potential protective effects of memantine + vitamin D against lysed or clotted blood in cortical neuronal cultures. We provide the first evidence that cortical axons in contact with lysed blood degenerate less after exposure to lysed blood in microfluidic neuronal cultures enriched with both memantine and vitamin D compared to control medium and cultures enriched with only memantine or only vitamin D. The reported synergistic neuroprotective effect of memantine + vitamin D, the combination originating an effect stronger than the sum, strongly encourages using both drugs following intracranial hemorrhage.