Evaluation of the Relationship between Pain Exposure and Somatosensory Evoked Potentials in Preterm Infants: A Prospective Cohort Study.

BACKGROUND AND AIM: First, to compare somatosensory evoked potentials (SEPs) in preterm newborns without major brain injury studied at term equivalent age (TEA) with a term historical control group. Second, to investigate the impact of pain exposure during the first 28 days after birth on SEPs. Third, to evaluate the association between SEPs and Bayley-III at 2 years corrected age (CA). METHODS: Infants born at <32 weeks' gestational age (GA) were studied with continuous-SEPs. First, SEP differences between preterm and term infants were analyzed. Second, regression analyses were conducted to explore the association between SEPs and painful procedures, and then between SEPs and neurodevelopment. RESULTS: 86 preterm infants were prospectively enrolled. Preterm infants exhibited prolonged N1 latencies, central conduction times (CCTs), lower N1-P1 amplitudes, and more recurrently abnormal SEPs compared to term infants. Higher pain exposure predicted longer N1 latency and slower CCT (all p < 0.005), adjusting for clinical risk factors. Younger GA and postmenstrual age (PMA) at SEP recording were associated with longer N1 latency and lower N1-P1 amplitude (all p < 0.005). A normal SEP at TEA positively predicted cognitive outcome at 2 years CA (p < 0.005). CONCLUSION: Pain exposure and prematurity were risk factors for altered SEP parameters at TEA. SEPs predicted cognitive outcome.

Morphine exposure and prematurity affect flash visual evoked potentials in preterm infants.

Objective: The present study aimed to explore first the impact of perinatal risk factors on flash-VEP waves and morphology in a group of preterm infants studied at term equivalent age (TEA). Second, to correlate VEP morphology with neurological outcome at 2 years corrected age (CA). Methods: Infants with a gestational age (GA) at birth <32 weeks, without major brain injury, were enrolled. Multivariate regression analyses were performed, and the models were run separately for each dependent variable N2, P2, N3 latencies and P2 amplitude. Logistic regression was applied to study N4 component (present/absent) and VEP morphology (regular/irregular). The predictors were GA, bronchopulmonary dysplasia (BPD), postmenstrual age at VEP registration, cumulative morphine and fentanyl dose, and painful procedures. Lastly, linear regression models were performed to assess the relation between the Bayley-III cognitive and motor scores at 2 years CA and VEP morphology, in relation to GA, BPD, painful procedures and cumulative morphine dose. Results: Eighty infants were enrolled. Morphine was the predictor of N2 (R2 = 0.09, p = 0.006), P2 (R2 = 0.11, p = 0.002), and N3 (R2 = 0.13, p = 0.003) latencies. Younger GA was associated with lower amplitude (R2 = 0.05, p = 0.029). None of the independent variables predicted the presence of N4 component, nor VEP morphology in the logistic analysis. VEP morphology was not associated with cognitive and motor scores at 2 years. Conclusions: Morphine treatment and prematurity were risk factors for altered VEPs parameters at TEA. In our cohort VEP morphology did not predict neurological outcome. Significance: Morphine administration should be evaluated according to potential risks and benefits, and dosage individually accustomed, according to pain and comfort scores, considering the possible risk for neurodevelopmental impairment.

Is the Patient State Index a reliable parameter as guide to anaesthesiology in cranial neurosurgery? A first intraoperative study and a literature review.

BACKGROUND: Patient State Index (PSI) and Suppression Ratio (SR) are two indices calculated by quantitative analysis of EEG used to estimate the depth of anaesthesia but their validation in neurosurgery must be done. Our aim was to investigate the congruity PSI and SR with raw EEG monitoring in neurosurgery. METHODS: We included 34 patients undergoing elective cranial neurosurgery. Each patient was monitored by a SedLine device (PSI and SR) and by raw EEG. To appraise the agreement between PSI, SR and EEG Suppr%, Bland-Altman analysis was used. We also correlated the PSI and SR recorded at different times during surgery to the degree of suppression of the raw EEG data by Spearman's rank correlation coefficient. For a comparison with previous data we made an international literature review according to PRISMA protocol. RESULTS: At all recording times, we found that there is a strong agreement between PSI and raw EEG. We also found a significant correlation for both PSI and SR with the EEG suppression percentage (p < 0.05), but with a broad dispersion of the individual values within the confidence interval. CONCLUSION: The Masimo SedLine processed EEG monitoring system can be used as a guide in the anaesthetic management of patients during elective cranial neurosurgery, but the anaesthesiologist must be aware that previous correlations between PSI and SR with the suppression percentage may not always be valid in all individual patients. The use of an extended visual raw EEG evaluated by an expert electroencephalographer might help to provide better guidance.

Feasibility of Intraoperative Visual Evoked Potential Monitoring by Cortical Strip Electrodes in Patients During Brain Surgery: A Preliminary Study.

OBJECTIVE: The role of visual evoked potentials (VEPs) monitoring during neurosurgical procedure in patient remains unclear. The purpose of our study was to determine the feasibility of intraoperative VEP recording using a strip cortical electrode during surgical resection of intracranial lesions. METHODS: In this prospective, monocentric, observational study, we enrolled consecutive patients undergoing neurosurgical procedure for intracranial lesions. After dural opening, a cortical strip was positioned on the lateral occipital surface. Flash VEPs were continuously recorded using both subdermal corkscrew electrodes and strip electrodes. An electroretinogram was also recorded to guarantee delivery of adequate flash stimuli to the retina. RESULTS: We included 10 patients affected by different intracranial lesions. Flash VEPs were recorded using subdermal corkscrew electrodes in all patients except 1 in whom they were never identified during the recording. Flash VEPs were recorded using strip electrodes in all patients and showed a polyphasic morphology with a significantly larger amplitude compared with that of flash VEPs measured using subdermal corkscrew electrodes. No patient reported worsened postoperative vision and a >50% decrease in the VEPs amplitude was never registered. CONCLUSIONS: We have reported for the first time in the literature that VEP monitoring during a neurosurgical procedure is feasible via a cortical strip located on the occipital surface. The technique demonstrated greater stability and a larger amplitude compared with recordings with scalp electrodes, facilitating identification of any changes. Studies with more patients are needed to assess the clinical reliability of the technique.

Aggregate Channel Features for newborn face detection in Neonatal Intensive Care Units.

An efficient face detector could be very helpful to point out possible neurological dysfunctions such as seizure events in Neonatal Intensive Care Units. However, its development is still challenging because large public datasets of newborns' faces are missing. Over the years several studies introduced semi-automatic approaches. This study proposes a fully automated face detector for newborns in Neonatal Intensive Care Units, based on the Aggregate Channel Feature algorithm. The developed method is tested on a dataset of video recordings from 42 full-term newborns collected at the Neuro-physiopathology and Neonatology Clinical Units, AOU Careggi, Firenze, Italy. The proposed system showed promising results, giving (mean ± standard error): log-Average Miss Rate = 0.47 ± 0.05 and Average Precision Recall = 0.61 ± 0.05. Moreover, achieved results highlighted interesting differences between newborns without seizures, newborns with electro-clinical seizures, and newborns with electrographic-only seizures. For both metrics statistically significant differences were found between patients with electro-clinical seizures and the other two groups. Clinical Relevance- The proposed method, based on quantitative physio-pathological features of facial movements, is of clinical relevance as it could speed up pain or seizure assessment of newborns in Neonatal Intensive Care Units.

Unilateral Transient Enhanced SEP during Integrated Multiparameter Neurophysiological Monitoring in a Newborn with Symptomatic Seizure.

During Integrated Multiparametric Neurophysiological Monitoring (IMNA), a newborn with suspected hypoxia at birth and microhaemorrhagic and ischaemic lesions presented some clonic-tonic episodes with specific EEG patterns characterized by rolandic and temporal spikes and the appearance of a unilateral enhanced Somatosensory Evoked Potential (SEP) (10.45 µv). Since the literature does not seem to describe cases of giant SEP in newborns, in this case report, we will discuss the hypotheses underlying this potential. It could be assumed that the ischaemic and haemorrhagic lesions presented by the newborn may have developed as a result of neurotransmitter balance failure. This may be the origin of the EEG picture, which, consequently, could have triggered a potential with high amplitude.

Heart Rate Variability Analysis for Seizure Detection in Neonatal Intensive Care Units.

In Neonatal Intensive Care Units (NICUs), the early detection of neonatal seizures is of utmost importance for a timely clinical intervention. Over the years, several neonatal seizure detection systems were proposed to detect neonatal seizures automatically and speed up seizure diagnosis, most based on the EEG signal analysis. Recently, research has focused on other possible seizure markers, such as electrocardiography (ECG). This work proposes an ECG-based NSD system to investigate the usefulness of heart rate variability (HRV) analysis to detect neonatal seizures in the NICUs. HRV analysis is performed considering time-domain, frequency-domain, entropy and multiscale entropy features. The performance is evaluated on a dataset of ECG signals from 51 full-term babies, 29 seizure-free. The proposed system gives results comparable to those reported in the literature: Area Under the Receiver Operating Characteristic Curve = 62%, Sensitivity = 47%, Specificity = 67%. Moreover, the system's performance is evaluated in a real clinical environment, inevitably affected by several artefacts. To the best of our knowledge, our study proposes for the first time a multi-feature ECG-based NSD system that also offers a comparative analysis between babies suffering from seizures and seizure-free ones.

Continous somatosensory evoked potentials and brain injury in neonatal hypoxic-ischaemic encephalopathy treated with hypothermia.

AIM: To explore whether continuous somatosensory evoked potentials (SEPs) monitoring and video electroencephalograms (VEEG) accurately predict lesions observed on brain magnetic resonance imaging (MRI) in neonates with hypoxic-ischaemic encephalopathy (HIE) receiving therapeutic hypothermia. METHOD: This prospective study included 31 neonates (16 males, 15 females; mean [SD] gestational age 39 weeks [1.67]) who received therapeutic hypothermia for HIE. Therapeutic hypothermia was provided for 72 hours, with a target temperature of 33.0°C to 34.0°C and this was followed by a rewarming rate of approximately 0.5°C per hour, up to 36.5°C. SEPs and VEEG were evaluated simultaneously and continuously for 1 hour under normothermic conditions. MRI was carried out at a mean (SD) age of 6 (2) days. RESULTS: Our results showed a statistically significant correlation between continuous SEP and MRI scores (r=0.37, p=0.03), but not between the VEEG and MRI scores (r=0.30, p=0.09). Receiver operating characteristic analysis confirmed that continuous SEPs were highly specific and sensitive at predicting MRI abnormalities, whereas the VEEG had high specificity but low sensitivity. INTERPRETATION: Continuous monitoring of SEPs could provide early and important prognostic information in neonates with HIE. WHAT THIS PAPER ADDS: Early continuous somatosensory evoked potential (SEP) monitoring is correlated with hypoxic-ischaemic encephalopathy (HIE) lesions. Video electroencephalograms (VEEGs) are associated with lesions diagnosed after magnetic resonance imaging. Both showed high specificity, but VEEGs did not show high sensitivity. Continuously monitoring SEPs provides important information about HIE.

Comparison of Sympathetic Skin Response (SSR) between Electrical and Acoustic Stimuli in a Healthy Pediatric Population.

Data in the literature report that latency and morphology in the cutaneous sympathetic skin response (SSR) do not change according to the type of stimulus delivered, unlike the amplitude which shows greater values in relation to the intensity of the physical impact caused in patient. Since the acoustic stimulus represents a method better tolerated by the pediatric patient, the aim of this study is to evaluate the presence or absence of significant differences in SSR between electrical and acoustic stimuli. The SSR was performed for each child of 18 recruited in this study, deriving from the palm of the hand and the sole of the foot and initially delivering an electrical stimulus at the level of the median nerve at the wrist. Two acoustic stimuli were subsequently delivered with the aid of audiometric headphones. Our results show no significant differences for the amplitude values obtained (p values > 0.05). For the latency there was a statistically significant difference (p-value = 0.001) for the left hand, subsequently not confirmed by the comparison performed between the two sides (p-values = 0.28 and 0.56). If these preliminary data are confirmed by a larger sample, the acoustic stimulus could be introduced in a standardized protocol for performing SSR in pediatric patients.

Electrodiagnostic findings in patients with non-COVID-19- and COVID-19-related acute respiratory distress syndrome.

BACKGROUND: Critical illness polyneuropathy and myopathy (CIPNM) is a frequent neurological manifestation in patients with acute respiratory distress syndrome (ARDS) from coronavirus disease 2019 (COVID-19) infection. CIPNM diagnosis is usually limited to clinical evaluation. We compared patients with ARDS from COVID-19 and other aetiologies, in whom a neurophysiological evaluation for the detection of CIPNM was performed. The aim was to determine if there were any differences between these two groups in frequency of CINPM and outcome at discharge from the intensive care unit (ICU). MATERIALS AND METHODS: This was a single-centre retrospective study performed on mechanically ventilated patients consecutively admitted (January 2016-June 2020) to the ICU of Careggi Hospital, Florence, Italy, with ARDS of different aetiologies. Neurophysiological evaluation was performed on patients with stable ventilation parameters, but marked widespread hyposthenia (Medical Research Council score <48). Creatine phosphokinase (CPK), lactic dehydrogenase (LDH) and mean morning glycaemic values were collected. RESULTS: From a total of 148 patients, 23 with COVID-19 infection and 21 with ARDS due to other aetiologies, underwent electroneurography/electromyography (ENG/EMG) recording. Incidence of CIPNM was similar in the two groups, 65% (15 of 23) in COVID-19 patients and 71% (15 of 21) in patients affected by ARDS of other aetiologies. At ICU discharge, subjects with CIPNM more frequently required ventilatory support, regardless the aetiology of ARDS. CONCLUSION: ENG/EMG represents a useful tool in the identification of the neuromuscular causes underlying ventilator wean failure and patient stratification. A high incidence of CIPNM, with a similar percentage, has been observed in ARDS patients of all aetiologies.

Muscle-ultrasound evaluation in healthy pediatric subjects: Age-related normative data.

INTRODUCTION: The muscle ultrasound examination (MUS) is a noninvasive and inexpensive technique for evaluating neuromyopathies. Standardized MUS normative data are incomplete in pediatric subjects. METHODS: We performed a MUS study with 120 healthy children (59 males; mean age, 10.44 years; age range, 2-16 years). We measured the width and the echogenicity bilaterally in the following muscles: biceps brachii and brachialis, brachioradialis, forearm-flexors, rectus femoris and vastus intermedius, tibialis anterior, extensor hallucis longus, lateral and medial gastrocnemius. RESULTS: The muscle thickness increased with age for all muscles. Confidence limits were set for each age group muscle width. Echogenicity increased with age only in some muscles. DISCUSSIONS: Our MUS study provides new data on physiological muscle structural changes in healthy children to address the limited available references in this age group. Muscle Nerve 58: 245-250, 2018.

Multimodal neurophysiological monitoring in healthy infants born at term: normative continuous somatosensory evoked potentials data.

AIM: To describe accurate, standardized 1h-multimodal neurophysiological monitoring (1h-MNM), while simultaneously recording VEEG, aEEG, and SEP-C bilaterally from median nerves, and to collect neonatal normative SEP-C data related to behavioural states. METHOD: Twenty healthy, term newborn infants (13 males, 7 females; gestational age 37-42wks; mean 39.6wks, standard deviation [SD] 1.3wks) underwent 1h-MNM within 2 days of life, with focus on recording of the SEP-C (band-pass setting 1-100 Hz, rate of stimulation 1.1 Hz, 50 alternate stimuli). RESULTS: 1h-MNM was easily obtained with identification of cervical (N13) and cortical (N1, P1) SEP-C responses in all infants. SEP-C minimal and maximum N1 latencies/N1-P1 amplitudes were identified, bilaterally, during periods of spontaneous sleep active-quiet-active (AS-QS-AS) and quiet-wakefulness. Minimal latencies and amplitudes occurred in 60% of active sleep/quiet-wakefulness, with the maximums in 70% of quiet sleep. The SEP-C mean values were latencies of N13=13.6ms (SD 1.4ms) and N1=33.6ms (SD 3.9ms) to 34.2ms (SD 4.8ms) in left and right hemisphere respectively; central-conduction-time (CCT) (N13-N1), 20.0ms (SD 4.3ms) to 20.6ms (SD 4.8ms); N1-P1 amplitude=4.6ms (SD 2.7ms) to 3.8µV (SD 2.2µV). INTERPRETATION: 1h-MNM can record simultaneously VEEG/aEEG/SEP-C in newborn infants, showing the modulation of SEP cortical responses in relation to behavioural states in all infants studied using an appropriate neonatal method. We emphasize the importance of obtaining neonatal SEP-C normative data to better identify pathological findings in neonatal brain injury.