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.

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.

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.

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.

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.

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.

Are neurophysiologic tests reliable, ultra-early prognostic indices after cardiac arrest?

OBJECTIVES: Determining early and reliable prognosis in comatose subjects after cardiac arrest is a central component of post-cardiac arrest care both for developing realistic prognostic expectations for families, and for better determining which resources are mobilized or withheld for individual patients. The aim of the study was to evaluate the prognostic accuracy of EEG and SEP patterns during the very early period (within the first 6 h) after cardiac arrest. METHODS: We retrospectively analysed comatose patients after CA, either inside or outside the hospital, in which prognostic evaluation was made during the first 6 h from CA. Prognostic evaluation comprised clinical evaluation (GCS and pupillary light reflex) and neurophysiological (electroencephalography (EEG) and somatosensory evoked potentials (SEP)) studies. Prognosis was evaluated with regards to likelihood of recovery of consciousness and also likelihood of failure to regain consciousness. RESULTS: Forty-one comatose patients after cardiac arrest were included. All patients with continuous and nearly continuous EEG recovered consciousness. Isoelectric EEG was always associated with poor outcome. Burst-suppression, suppression and discontinuous patterns were usually associated with poor outcome although some consciousness recovery was observed. Bilaterally absent SEP responses were always associated with poor outcome. Continuous and nearly continuous EEG patterns were never associated with bilaterally absent SEP. CONCLUSIONS: During the very early period following cardiac arrest (first 6 h), EEG and SEP maintain their high predictive value to predict respectively recovery and failure of recovery of consciousness. A very early EEG exam allows identification of patients with very high probability of a good outcome, allowing rapid use of the most appropriate therapeutic procedures.

A randomised, double-blind, sham-controlled study of left prefrontal cortex 15 Hz repetitive transcranial magnetic stimulation in cocaine consumption and craving.

BACKGROUND: Cocaine use disorder (CUD) is a global health issue with no effective treatment. Repetitive Transcranial Magnetic Stimulation (rTMS) is a recently proposed therapy for CUD. METHODS: We conducted a single-center, randomised, sham-controlled, blinded, parallel-group research with patients randomly allocated to rTMS (15 Hz) or Sham group (1:1) using a computerised block randomisation process. We enrolled 62 of 81 CUD patients in two years. Patients were followed for eight weeks after receiving 15 15 Hz rTMS/sham sessions over the left dorsolateral prefrontal cortex (DLPFC) during the first three weeks of the study. We targeted the DLFPC following the 5 cm method. Cocaine lapses in twice a week urine tests were the primary outcome. The secondary outcomes were craving severity, cocaine use pattern, and psychometric assessments. FINDINGS: We randomly allocated patients to either an active rTMS group (32 subjects) or a sham treatment group (30 subjects). Thirteen (42%) and twelve (43.3%) of the subjects in rTMS and sham groups, respectively, completed the full trial regimen, displaying a high dropout rate. Ten/30 (33%) of rTMS-treated patients tested negative for cocaine in urine, in contrast to 4/27 of placebo controls (p = 0.18, odd ratio 2.88, CI 0.9-10). The Kaplan-Meier survival curve did not state a significant change between the treated and sham groups in the time of cocaine urine negativisation (p = 0.20). However, the severity of cocaine-related cues mediated craving (VAS peak) was substantially decreased in the rTMS treated group (p<0.03) after treatment at T1, corresponding to the end of rTMS treatment. Furthermore, in the rTMS and sham groups, self-reported days of cocaine use decreased significantly (p<0.03). Finally, psychometric impulsivity parameters improved in rTMS-treated patients, while depression scales improved in both groups. CONCLUSIONS: In CUD, rTMS could be a useful tool for lowering cocaine craving and consumption. TRIAL REGISTRATION: The study number on clinicalTrials.gov is NCT03607591.

Amplitude Instability of Somatosensory Evoked Potentials as an Indicator of Delayed Cerebral Ischemia in a Case of Subarachnoid Hemorrhage.

We describe a 55-year-old male patient with a subarachnoid hemorrhage (SAH) as a result of left middle cerebral artery (MCA) aneurysm rupture, who underwent continuous electroencephalogram (EEG) and somatosensory evoked potential (cEEG-SEP) monitoring that showed an unusual SEP trend pattern. EEG was continuously recorded, and SEPs following stimulation of median nerves were recorded every 50 minutes, with the amplitude and latency of the cortical components automatically trended. An increase in intracranial pressure required a left decompressive craniectomy. cEEG-SEP monitoring was started on day 7, which showed a prolonged (24 hours) instability of SEPs in the left hemisphere. During this phase, left MCA vasospasm was demonstrated by transcranial Doppler (TCD), and computed tomography perfusion (CTP) showed a temporo-parieto-occipital ischemic penumbra. Following intravascular treatment, hypoperfusion and the amplitude of cortical SEPs improved. In our case, a prolonged phase of SEP amplitude instability during vasospasm in SAH correlated with a phase of ischemic penumbra, as demonstrated by CTP. In SAH, SEP instability during continuous monitoring is a pattern of alert that can allow treatments capable of avoiding irreversible neurological deterioration.

Efficacy of high-frequency (15Hz) repetitive transcranial magnetic stimulation (rTMS) of the left premotor cortex/dorsolateral prefrontal cortex in decreasing cocaine intake (the MagneTox study): A study protocol for a randomized placebo-controlled pilot trial.

BACKGROUND: Cocaine use disorder (CUD) is very common and has psychological and physical consequences. Patients with CUD present hypoactivity of the prefrontal cortical area. Thus, excitatory repetitive transcranial magnetic stimulation (rTMS) targeting the premotor cortex/dorsolateral prefrontal cortex (PMC/DLPFC), given its ability to increase prefrontal area excitability and to modulate cortico-limbic activity, could result in a decrease in cocaine intake. METHODS: We designed a protocol for a monocentric, randomized, double-blind, placebo-controlled, parallel-group pilot trial, with the principal aim of assessing the efficacy of rTMS on the reduction of cocaine intake. Patients with CUD will be recruited according to inclusion and exclusion criteria, and then randomized to undergo active or sham rTMS. Our rTMS protocol will consist of 15 days of 15Hz rTMS targeting the left PMC/DLPFC. Toxicological and psychiatric assessments, urine drug tests, the Cocaine Craving Questionnaire (CCQ) and the Visual Analogic Scale (VAS) will be used to assess changes from baseline in cocaine intake and craving, mood and quality of life. DISCUSSION: Only a few studies have evaluated the efficacy of rTMS for CUD treatment in humans, with limitations concerning small sample size, short treatment duration, different rTMS protocols and the absence of a placebo-controlled group. Our study will attempt to overcome these shortcomings and will provide data that can be used for future larger studies of non-invasive left PMC/DLPFC stimulation as a treatment for CUD.

Time-dependent and independent neurophysiological indicators of prognosis in post-anoxic coma subjects treated by therapeutic hypothermia.

BACKGROUND: Evaluation of prognostic value of electroencephalography (EEG) and somatosensory evoked potentials (SEP) according to different recording times. METHODS: A retrospective cohort study performed at the medical ICU of the AOU Careggi Teaching Hospital (Florence, Italy) of comatose adults (>18 years) after cardiac arrest (CA) and treated with therapeutic hypothermia (TH). We evaluated the Glasgow Coma Scale, EEG, and SEP performed at 12, 24, and 72 hrs after CA. Outcome was determined by the Glasgow Outcome Scale at 6 months after CA. RESULTS: We analyzed 167 patients. All patients with grade 1 EEG ("continuous") within 12 hours of CA recovered consciousness (false positive rate: 0.0%). Grade 2 EEG ("non-continuous") at 72 hours predicted a poor outcome with FPR=0.0%. Bilateral absent SEP at any time after CA predicted a poor outcome. CONCLUSIONS: EEG is a reliable time-dependent predictor of a good outcome (within 12 hours) and a poor outcome (after 72 hours). SEP is a time-independent predictor of a poor outcome.