Thalamocortical coherence and causality in different sleep stages using deep brain stimulation recordings.

Previous research has shown an interplay between the thalamus and cerebral cortex during NREM sleep in humans, however the directionality of the thalamocortical synchronization is as yet unknown. In this study thalamocortical connectivity during different NREM sleep stages using sleep scalp electroencephalograms and local field potentials from the left and right anterior thalamus was measured in three epilepsy patients implanted with deep brain stimulation electrodes. Connectivity was assessed as debiased weighted phase lag index and granger causality between the thalamus and cortex for the NREM sleep stages N1, N2 and N3. Results showed connectivity was most prominently directed from cortex to thalamus. Moreover, connectivity varied in strength between the different sleep stages, but barely in direction or frequency. These results imply relatively stable thalamocortical connectivity during NREM sleep directed from the cortex to the thalamus.

Assessment of need for hemostatic evaluation in patients taking valproic acid: A retrospective cross-sectional study.

INTRODUCTION: Valproic acid (VPA) is a frequently prescribed anti-epileptic drug. Since its introduction side effects on hemostasis are reported. However, studies show conflicting results, and the clinical relevance is questioned. We aimed to determine the coagulopathies induced by VPA in patients who undergo high-risk surgery. The study results warrant attention to this issue, which might contribute to reducing bleeding complications in future patients. METHODS: Between January 2012 and August 2020, 73 consecutive patients using VPA were retrospectively included. Extensive laboratory hemostatic assessment (including platelet function tests) was performed before elective high-risk surgery. Patient characteristics, details of VPA treatment, and laboratory results were extracted from medical records. RESULTS: 46.6% of the patients using VPA (n = 73) showed coagulopathy. Mainly, platelet function disorder was found (36.4%). Thrombocytopenia was seen in 9.6% of the patients. Data suggested that the incidence of coagulopathies was almost twice as high in children as compared to adults and hypofibrinogenemia was only demonstrated in children. No association was found between the incidence of coagulopathies and VPA dosage (mg/kg/day). CONCLUSION: A considerable number of patients using VPA were diagnosed with coagulopathy, especially platelet function disorder. Further prospective studies are needed to confirm the need for comprehensive laboratory testing before elective high-risk surgery in these patients.

Treating Rhythmic and Periodic EEG Patterns in Comatose Survivors of Cardiac Arrest.

BACKGROUND: Whether the treatment of rhythmic and periodic electroencephalographic (EEG) patterns in comatose survivors of cardiac arrest improves outcomes is uncertain. METHODS: We conducted an open-label trial of suppressing rhythmic and periodic EEG patterns detected on continuous EEG monitoring in comatose survivors of cardiac arrest. Patients were randomly assigned in a 1:1 ratio to a stepwise strategy of antiseizure medications to suppress this activity for at least 48 consecutive hours plus standard care (antiseizure-treatment group) or to standard care alone (control group); standard care included targeted temperature management in both groups. The primary outcome was neurologic outcome according to the score on the Cerebral Performance Category (CPC) scale at 3 months, dichotomized as a good outcome (CPC score indicating no, mild, or moderate disability) or a poor outcome (CPC score indicating severe disability, coma, or death). Secondary outcomes were mortality, length of stay in the intensive care unit (ICU), and duration of mechanical ventilation. RESULTS: We enrolled 172 patients, with 88 assigned to the antiseizure-treatment group and 84 to the control group. Rhythmic or periodic EEG activity was detected a median of 35 hours after cardiac arrest; 98 of 157 patients (62%) with available data had myoclonus. Complete suppression of rhythmic and periodic EEG activity for 48 consecutive hours occurred in 49 of 88 patients (56%) in the antiseizure-treatment group and in 2 of 83 patients (2%) in the control group. At 3 months, 79 of 88 patients (90%) in the antiseizure-treatment group and 77 of 84 patients (92%) in the control group had a poor outcome (difference, 2 percentage points; 95% confidence interval, -7 to 11; P = 0.68). Mortality at 3 months was 80% in the antiseizure-treatment group and 82% in the control group. The mean length of stay in the ICU and mean duration of mechanical ventilation were slightly longer in the antiseizure-treatment group than in the control group. CONCLUSIONS: In comatose survivors of cardiac arrest, the incidence of a poor neurologic outcome at 3 months did not differ significantly between a strategy of suppressing rhythmic and periodic EEG activity with the use of antiseizure medication for at least 48 hours plus standard care and standard care alone. (Funded by the Dutch Epilepsy Foundation; TELSTAR ClinicalTrials.gov number, NCT02056236.).

Influence of Anesthesia and Clinical Variables on the Firing Rate, Coefficient of Variation and Multi-Unit Activity of the Subthalamic Nucleus in Patients with Parkinson's Disease.

BACKGROUND: Microelectrode recordings (MER) are used to optimize lead placement during subthalamic nucleus deep brain stimulation (STN-DBS). To obtain reliable MER, surgery is usually performed while patients are awake. Procedural sedation and analgesia (PSA) is often desirable to improve patient comfort, anxiolysis and pain relief. The effect of these agents on MER are largely unknown. The objective of this study was to determine the effects of commonly used PSA agents, dexmedetomidine, clonidine and remifentanil and patient characteristics on MER during DBS surgery. METHODS: Data from 78 patients with Parkinson's disease (PD) who underwent STN-DBS surgery were retrospectively reviewed. The procedures were performed under local anesthesia or under PSA with dexmedetomidine, clonidine or remifentanil. In total, 4082 sites with multi-unit activity (MUA) and 588 with single units were acquired. Single unit firing rates and coefficient of variation (CV), and MUA total power were compared between patient groups. RESULTS: We observed a significant reduction in MUA, an increase of the CV and a trend for reduced firing rate by dexmedetomidine. The effect of dexmedetomidine was dose-dependent for all measures. Remifentanil had no effect on the firing rate but was associated with a significant increase in CV and a decrease in MUA. Clonidine showed no significant effect on firing rate, CV or MUA. In addition to anesthetic effects, MUA and CV were also influenced by patient-dependent variables. CONCLUSION: Our results showed that PSA influenced neuronal properties in the STN and the dexmedetomidine (DEX) effect was dose-dependent. In addition, patient-dependent characteristics also influenced MER.

Combining Gamma With Alpha and Beta Power Modulation for Enhanced Cortical Mapping in Patients With Focal Epilepsy.

About one third of patients with epilepsy have seizures refractory to the medical treatment. Electrical stimulation mapping (ESM) is the gold standard for the identification of "eloquent" areas prior to resection of epileptogenic tissue. However, it is time-consuming and may cause undesired side effects. Broadband gamma activity (55-200 Hz) recorded with extraoperative electrocorticography (ECoG) during cognitive tasks may be an alternative to ESM but until now has not proven of definitive clinical value. Considering their role in cognition, the alpha (8-12 Hz) and beta (15-25 Hz) bands could further improve the identification of eloquent cortex. We compared gamma, alpha and beta activity, and their combinations for the identification of eloquent cortical areas defined by ESM. Ten patients with intractable focal epilepsy (age: 35.9 ± 9.1 years, range: 22-48, 8 females, 9 right handed) participated in a delayed-match-to-sample task, where syllable sounds were compared to visually presented letters. We used a generalized linear model (GLM) approach to find the optimal weighting of each band for predicting ESM-defined categories and estimated the diagnostic ability by calculating the area under the receiver operating characteristic (ROC) curve. Gamma activity increased more in eloquent than in non-eloquent areas, whereas alpha and beta power decreased more in eloquent areas. Diagnostic ability of each band was close to 0.7 for all bands but depended on multiple factors including the time period of the cognitive task, the location of the electrodes and the patient's degree of attention to the stimulus. We show that diagnostic ability can be increased by 3-5% by combining gamma and alpha and by 7.5-11% when gamma and beta were combined. We then show how ECoG power modulation from cognitive testing can be used to map the probability of eloquence in individual patients and how this probability map can be used in clinical settings to optimize ESM planning. We conclude that the combination of gamma and beta power modulation during cognitive testing can contribute to the identification of eloquent areas prior to ESM in patients with refractory focal epilepsy.

Preterm Perinatal Hypoxia-Ischemia Does not Affect Somatosensory Evoked Potentials in Adult Rats.

Somatosensory evoked potentials (SSEPs) are a valuable tool to assess functional integrity of the somatosensory pathways and for the prediction of sensorimotor outcome in perinatal injuries, such as perinatal hypoxia-ischemia (HI). In the present research, we studied the translational potential of SSEPs together with sensory function in the male adult rat with perinatal HI compared to the male healthy adult rat. Both somatosensory response and evoked potential were measured at 10-11 months after global perinatal HI. Clear evoked potentials were obtained, but there were no group differences in the amplitude or latency of the evoked potentials of the preceding sensory response. The bilateral tactile stimulation test was also normal in both groups. This lack of effect may be ascribed to the late age-of-testing and functional recovery of the rats.

Single-Cell Recordings to Target the Anterior Nucleus of the Thalamus in Deep Brain Stimulation for Patients with Refractory Epilepsy.

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a promising treatment for patients with refractory epilepsy. However, therapy response varies and precise positioning of the DBS lead is potentially essential for maximizing therapeutic efficacy. We investigate if single-cell recordings acquired by microelectrode recordings can aid targeting of the ANT during surgery and hypothesize that the neuronal firing properties of the target region relate to clinical outcome. We prospectively included 10 refractory epilepsy patients and performed microelectrode recordings under general anesthesia to identify the change in neuronal signals when approaching and transecting the ANT. The neuronal firing properties of the target region, anatomical locations of microelectrode recordings and active contact positions of the DBS lead along the recorded trajectory were compared between responders and nonresponders to DBS. We obtained 19 sets of recordings from 10 patients (five responders and five nonresponders). Amongst the 403 neurons detected, 365 (90.6%) were classified as bursty. Entry into the ANT was characterized by an increase in firing rate while exit of the ANT was characterized by a decrease in firing rate. Comparing the trajectories of responders to nonresponders, we found differences neither in the neuronal firing properties themselves nor in their locations relative to the position of the active contact. Single-cell firing rate acquired by microelectrode recordings under general anesthesia can thus aid targeting of the ANT during surgery, but is not related to clinical outcome in DBS for patients with refractory epilepsy.

The Use of Continuous EEG Monitoring in Intensive Care Units in The Netherlands: A National Survey.

BACKGROUND: Currently, continuous electroencephalographic monitoring (cEEG) is the only available diagnostic tool for continuous monitoring of brain function in intensive care unit (ICU) patients. Yet, the exact relevance of routinely applied ICU cEEG remains unclear, and information on the implementation of cEEG, especially in Europe, is scarce. This study explores current practices of cEEG in adult Dutch ICU departments focusing on organizational and operational factors, development over time and factors perceived relevant for abstaining its use. METHODS: A national survey on cEEG in adults among the neurology and adult intensive care departments of all Dutch hospitals (n = 82) was performed. RESULTS: The overall institutional response rate was 78%. ICU cEEG is increasingly used in the Netherlands (in 37% of all hospitals in 2016 versus in 21% in 2008). Currently in 88% of university, 55% of teaching and 14% of general hospitals use ICU cEEG. Reasons for not performing cEEG are diverse, including perceived non-feasibility and lack of data on the effect of cEEG use on patient outcome. Mostly, ICU cEEG is used for non-convulsive seizures or status epilepticus and prognostication. However, cEEG is never or rarely used for monitoring cerebral ischemia and raised intracranial pressure in traumatic brain injury. Review and reporting practices differ considerably between hospitals. Nearly all hospitals perform non-continuous review of cEEG traces. Methods for moving toward continuous review of cEEG traces are available but infrequently used in practice. CONCLUSIONS: cEEG is increasingly used in Dutch ICUs. However, cEEG practices vastly differ between hospitals. Future research should focus on uniform cEEG practices including unambiguous EEG interpretation to facilitate collaborative research on cEEG, aiming to provide improved standard patient care and robust data on the impact of cEEG use on patient outcome.

Continuous electroencephalographic-monitoring in the ICU: an overview of current strengths and future challenges.

PURPOSE OF REVIEW: In ICUs, numerous physiological parameters are continuously monitored and displayed. Yet, functional monitoring of the organ of primary concern, the brain, is not routinely performed. Despite the benefits of ICU use of continuous electroencephalographic (EEG)-monitoring (cEEG) is increasingly recognized, several issues nevertheless seem to hamper its widespread clinical implementation. RECENT FINDINGS: Utilization of ICU cEEG has significantly improved detection and characterization of cerebral pathology, prognostication and clinical management in specific patient groups. Potential solutions to several remaining challenges are currently being established. Descriptive EEG-terminology is evolving, whereas logistical issues are dealt with using telemedicine and quantitative EEG trends, training of nonexpert personnel and development of specialized detection algorithms. These concerted solutions are advancing cEEG-registration towards cEEG-monitoring. Notwithstanding these advances, obstacles such as ambiguous EEG-interpretation and differences in treatment based on EEG-findings need yet to be overcome. SUMMARY: In selected critically ill patient groups, ICU cEEG has clear benefits over (repeated) standard EEG or no functional brain monitoring at all and if available, cEEG should be used. However, several issues preventing optimal ICU cEEG usage persist and should be further explored.

Deterioration of dyslexia after non-dominant temporal lobectomy for drug-resistant epilepsy.

We present a patient with drug-resistant right-sided temporal lobe epilepsy, caused by a ganglioglioma of the parahippocampal gyrus. Preoperatively, the patient was also known to have dyslexia. A right-sided anterior temporal lobectomy, including complete lesionectomy, was performed. Several months after the otherwise uncomplicated procedure, the patient complained about visual memory disturbances, accompanied by increased reading and spelling problems. Postoperative neuropsychological examination revealed deterioration of the visual memory functions, compared to the preoperative assessment, and consequently provided a possible explanation for worsening of the pre-existing dyslexia. In this case report, we hypothesize on the cause of this unusual deterioration and present recommendations to be included in the preoperative epilepsy surgery evaluation for patients with verbal or reading disorders such as dyslexia.

Automatic burst detection for the EEG of the preterm infant.

To aid with prognosis and stratification of clinical treatment for preterm infants, a method for automated detection of bursts, interburst-intervals (IBIs) and continuous patterns in the electroencephalogram (EEG) is developed. Results are evaluated for preterm infants with normal neurological follow-up at 2 years. The detection algorithm (MATLAB®) for burst, IBI and continuous pattern is based on selection by amplitude, time span, number of channels and numbers of active electrodes. Annotations of two neurophysiologists were used to determine threshold values. The training set consisted of EEG recordings of four preterm infants with postmenstrual age (PMA, gestational age + postnatal age) of 29-34 weeks. Optimal threshold values were based on overall highest sensitivity. For evaluation, both observers verified detections in an independent dataset of four EEG recordings with comparable PMA. Algorithm performance was assessed by calculation of sensitivity and positive predictive value. The results of algorithm evaluation are as follows: sensitivity values of 90% ± 6%, 80% ± 9% and 97% ± 5% for burst, IBI and continuous patterns, respectively. Corresponding positive predictive values were 88% ± 8%, 96% ± 3% and 85% ± 15%, respectively. In conclusion, the algorithm showed high sensitivity and positive predictive values for bursts, IBIs and continuous patterns in preterm EEG. Computer-assisted analysis of EEG may allow objective and reproducible analysis for clinical treatment.

Safety and one-year efficacy of intrathecal baclofen therapy in children with intractable spastic cerebral palsy.

BACKGROUND: Prospective studies that address both efficacy and safety of continuous infusion of intrathecal baclofen (CITB) in children with spastic cerebral palsy (CP), and that use outcome measures beyond muscle tone are lacking. AIMS: To study the efficacy at 12 months and safety up to 24 months after start of CITB in children with intractable spastic CP. METHODS: Nine girls and eight boys, aged 13.7 years (SD 2.9), received a SynchroMed pump for CITB. We prospectively recorded effects and adverse events at regular follow-up visits up to 24 months. Outcome measures included the 0-10 visual analogue scale (VAS) for individual problems, Gross Motor Function Measure (GMFM) and health related quality of life as measured with the Child Health Questionnaire-PF50. RESULTS: CITB for 12 months significantly improved the VAS for individual problems with 4.7 (SD 2.0; p=0.000), VAS for ease of care with 5.2 (SD 2.1; p=0.000), VAS for pain with 5.4 (SD 2.7; p=0.002); GMFM sitting dimension with 3.3 (range -4.0 to 22.0; p=0.022), GMFM goal dimension with 4.0 (range 0.0-26.0; p=0.007); and Child Health Questionnaire-PF50 domains of bodily pain/discomfort with 25.6 (SD 35.9; p=0.016) and mental health with 9.8 (SD 11.3; p=0.007). During a mean follow-up of 18.4 months (range 12-24), we recorded 80 adverse events. Eight adverse events were serious, but not life-threatening. CONCLUSIONS: CITB was effective at 12 months and safe up to 24 months for carefully selected children with intractable spastic CP. CITB relieved pain, facilitated ease of care and improved mental health. The majority of children could extend their activities and participation.

Inverted fixation-off sensitivity in atypical benign partial epilepsy.

Fixation-off sensitivity is an electroencephalographic phenomenon characterized by spike-and-wave discharges that only occur when central vision and fixation are eliminated. It is especially seen in children with Panayiotopoulos-type, early-onset, benign childhood occipital epilepsy or Gastaut type, late-onset, childhood occipital epilepsy. It can also be seen in eyelid myoclonia with absences, in other idiopathic generalized epilepsies, and in asymptomatic children without epilepsy. We describe a boy with atypical, benign partial epilepsy of childhood who exhibited the reverse: epileptiform activity that was suppressed by the absence of central vision or fixation, and activated by central vision or fixation.

Isolated spinal accessory neuropathy in an adolescent: a case study.

We describe a case of dynamic scapular winging due to trapezius muscle paresis following a sport-related injury of the accessory nerve. The typical clinical findings related to the peripheral nerve involved, the importance of neurophysiologic work-up, and possibilities for treatment are discussed.

Folinic acid-responsive seizures initially responsive to pyridoxine.

This report presents a male who developed clonic seizures on the day he was born. The next day, the diagnosis of pyridoxine-dependent seizures was made. However, contradictory to this diagnosis, seizures reappeared despite treatment with pyridoxine. Seizures ceased after folinic acid was initiated. The clinical and biochemical characteristics of folinic acid-responsive seizures are reviewed. Treatment with folinic acid should be considered in neonatal seizures of unknown origin that do not respond to pyridoxine, or manifest a transient response to pyridoxine.

Differential effects of subthalamic nucleus stimulation in advanced Parkinson disease on reaction time performance.

The aim of the present study was to assess the effect of bilateral subthalamic nucleus (STN) stimulation and dopaminergic medication on speed of mental processing and motor function. Thirty-nine patients suffering from advanced Parkinson disease (PD) were operated on. Motor function and reaction time (RT) performance [simple RT (SRT) and complex RT (CRT)] were evaluated under four experimental conditions with stimulation (stim) and medication (med) on and off: stim-on/med-on, stim-on/med-off, stim-off/med-off and stim-off/med-on. In the last condition, the patients received either low medication (usual dose) or high medication (suprathreshold dose). STN stimulation improved the motor performance in the SRT and CRT tasks. Furthermore, STN deep brain stimulation (DBS) also improved response preparation as shown by the significant improvement of the RT performance in the SRT task. This effect of STN DBS on the RT performance in the SRT task was greater as compared with the CRT task. This is due to the more complex information processing that is required in the CRT task as compared to the SRT task. These data suggest that treatment of STN hyperactivity by DBS improves motor function, confirming earlier reports, but has a differential effect on cognitive functions. The STN seems to be an important modulator of cognitive processing and STN DBS can differentially affect motor and associative circuits.