Quantitative Characterization of Rhythmic and Periodic EEG Patterns in Patients in a Coma After Cardiac Arrest and Association With Outcome.

OBJECTIVES: Rhythmic and periodic patterns (RPPs) on EEG in patients in a coma after cardiac arrest are associated with a poor neurologic outcome. We characterize RPPs using qEEG in relation to outcomes. METHODS: Post hoc analysis was conducted on 172 patients in a coma after cardiac arrest from the TELSTAR trial, all with RPPs. Quantitative EEG included corrected background continuity index (BCI*), relative discharge power (RDP), discharge frequency, and shape similarity. Neurologic outcomes at 3 months after arrest were categorized as poor (CPC = 3-5) or good (CPC = 1-2). RESULTS: A total of 16 patients (9.3%) had a good outcome. Patients with good outcomes showed later RPP onset (28.5 vs 20.1 hours after arrest, p < 0.05) and higher background continuity at RPP onset (BCI* = 0.83 vs BCI* = 0.59, p < 0.05). BCI* <0.45 at RPP onset, maximum BCI* <0.76, RDP >0.47, or shape similarity >0.75 were consistently associated with poor outcomes, identifying 36%, 22%, 40%, or 24% of patients with poor outcomes, respectively. In patients meeting both BCI* >0.44 at RPP onset and BCI* >0.75 within 72 hours, the probability of good outcomes doubled to 18%. DISCUSSION: Sufficient EEG background continuity before and during RPPs is crucial for meaningful recovery. Background continuity, discharge power, and shape similarity can help select patients with relevant chances of recovery and may guide treatment. TRIAL REGISTRATION INFORMATION: February 4, 2014, ClinicalTrial.gov, NCT02056236.

What Do You See? Signature Pedagogy in Continuous Electroencephalography Teaching.

PURPOSE: Electroencephalography (EEG) is commonly used in neurology, but there is variability in how neurologists interpret EEGs, potentially from variability in EEG teaching. Little is known about how EEG teaching is done to prepare neurologists for professional practice. METHODS: We interviewed a group of EEG experts to characterize their teaching practices around continuous EEG (cEEG). We used signature pedagogy as a framework to analyze and interpret the data. RESULTS: We identified pervasive and characteristic forms of cEEG teaching. Teaching is based on apprenticeship, relying on "learning by doing" in the context of real-life clinical practice. There are habitual steps that learners take to anchor teaching, which typically occurs during rounds. There is a common language and core knowledge that trainees need to master early in their training. CONCLUSIONS: There are pervasive characteristic forms of cEEG teaching. These findings can help facilitate instructional design and implementation of complementary or enhanced cEEG teaching practices.

Myoclonus in comatose patients with electrographic status epilepticus after cardiac arrest: Corresponding EEG patterns, effects of treatment and outcomes.

OBJECTIVE: To clarify the significance of any form of myoclonus in comatose patients after cardiac arrest with rhythmic and periodic EEG patterns (RPPs) by analyzing associations between myoclonus and EEG pattern, response to anti-seizure medication and neurological outcome. DESIGN: Post hoc analysis of the prospective randomized Treatment of ELectroencephalographic STatus Epilepticus After Cardiopulmonary Resuscitation (TELSTAR) trial. SETTING: Eleven ICUs in the Netherlands and Belgium. PATIENTS: One hundred and fifty-seven adult comatose post-cardiac arrest patients with RPPs on continuous EEG monitoring. INTERVENTIONS: Anti-seizure medication vs no anti-seizure medication in addition to standard care. MEASUREMENTS AND MAIN RESULTS: Of 157 patients, 98 (63%) had myoclonus at inclusion. Myoclonus was not associated with one specific RPP type. However, myoclonus was associated with a smaller probability of a continuous EEG background pattern (48% in patients with vs 75% without myoclonus, odds ratio (OR) 0.31; 95% confidence interval (CI) 0.16-0.64) and earlier onset of RPPs (24% vs 9% within 24 hours after cardiac arrest, OR 3.86;95% CI 1.64-9.11). Myoclonus was associated with poor outcome at three months, but not invariably so (poor neurological outcome in 96% vs 82%, p = 0.004). Anti-seizure medication did not improve outcome, regardless of myoclonus presence (6% good outcome in the intervention group vs 2% in the control group, OR 0.33; 95% CI 0.03-3.32). CONCLUSIONS: Myoclonus in comatose patients after cardiac arrest with RPPs is associated with poor outcome and discontinuous or suppressed EEG. However, presence of myoclonus does not interact with the effects of anti-seizure medication and cannot predict a poor outcome without false positives.

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.

Spatiotemporal patterns of sleep spindle activity in human anterior thalamus and cortex.

Sleep spindles (8 - 16 Hz) are transient electrophysiological events during non-rapid eye movement sleep. While sleep spindles are routinely observed in the cortex using scalp electroencephalography (EEG), recordings of their thalamic counterparts have not been widely studied in humans. Based on a few existing studies, it has been hypothesized that spindles occur as largely local phenomena. We investigated intra-thalamic and thalamocortical spindle co-occurrence, which may underlie thalamocortical communication. We obtained scalp EEG and thalamic recordings from 7 patients that received bilateral deep brain stimulation (DBS) electrodes to the anterior thalamus for the treatment of drug resistant focal epilepsy. Spindles were categorized into subtypes based on their main frequency (i.e., slow (10±2 Hz) or fast (14±2 Hz)) and their level of thalamic involvement (spanning one channel, or spreading uni- or bilaterally within the thalamus). For the first time, we contrasted observed spindle patterns with permuted data to estimate random spindle co-occurrence. We found that multichannel spindle patterns were systematically coordinated at the thalamic and thalamocortical level. Importantly, distinct topographical patterns of thalamocortical spindle overlap were associated with slow and fast subtypes of spindles. These observations provide further evidence for coordinated spindle activity in thalamocortical networks.

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.).

Predictive value of functional MRI and EEG in epilepsy diagnosis after a first seizure.

It is often difficult to predict seizure recurrence in subjects who have suffered a first-ever epileptic seizure. In this study, the predictive value of physiological signals measured using Electroencephalography (EEG) and functional MRI (fMRI) is assessed. In particular those patients developing epilepsy (i.e. a second unprovoked seizure) that were initially evaluated as having a low risk of seizure recurrence are of interest. In total, 26 epilepsy patients, of which 8 were initially evaluated as having a low risk of seizure recurrence (i.e. converters), and 17 subjects with only a single seizure were included. All subjects underwent routine EEG as well as fMRI measurements. For diagnostic classification, features related to the temporal dynamics were determined for both the processed EEG and fMRI data. Subsequently, a logistic regression classifier was trained on epilepsy and first-seizure subjects. The trained model was tested using the clinically relevant converters group. The sensitivity, specificity, and AUC (mean ±â€¯SD) of the regression model including metrics from both modalities were 74 ±â€¯19%, 82 ±â€¯18%, and 0.75 ±â€¯0.12, respectively. Positive and negative predictive values (mean ±â€¯SD) of the regression model with both EEG and fMRI features are 84 ±â€¯14% and 78 ±â€¯12%. Moreover, this EEG/fMRI model showed significant improvements compared to the clinical diagnosis, whereas the models using metrics from either EEG or fMRI do not reach significance (p > 0.05). Temporal metrics computationally derived from EEG and fMRI time signals may clinically aid and synergistically improve the predictive value in a first-seizure sample.

The association between surgical characteristics and cognitive decline following deep brain stimulation of the subthalamic nucleus in Parkinson's disease.

OBJECTIVE: Despite optimal improvement in motor functioning, both short- and long-term studies have reported small but consistent changes in cognitive functioning following STN-DBS in Parkinson's disease (PD). The aim of the present study was to explore whether surgical characteristics were associated with cognitive decline one year following STN-DBS. METHODS: We retrospectively analyzed 49 PD patients who underwent bilateral STN-DBS. Cognitive change scores were related to the number of microelectrode recording (MER) trajectories, the STN length as measured by MER, and cortical entry points. Regression analyses were corrected for age at surgery, disease duration, education and preoperative levodopa responsiveness. Patients were then divided into a cognitive and non-cognitive decline group for each neuropsychological test and compared regarding demographic and surgical characteristics. RESULTS: One year postoperatively, significant declines were found in verbal fluency, Stroop Color-Word test and Trail Making Test B (TMT-B). Only changes in TMT-B were associated with the coronal entry point in the right hemisphere. The number of MER trajectories and STN length were not associated with cognitive change scores. When comparing the cognitive decline and non-cognitive decline groups, no significant differences were found in surgical characteristics. CONCLUSIONS: The electrode passage through the right prefrontal lobe may contribute to subtle changes in executive function. However, only few patients showed clinically relevant cognitive decline. The use of multiple MER trajectories and a longer STN length were not associated with cognitive decline one year following surgery. From a cognitive point of view, DBS may be considered a relatively safe procedure.

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.

Sensorimotor Representation of Speech Perception. Cross-Decoding of Place of Articulation Features during Selective Attention to Syllables in 7T fMRI.

Sensorimotor integration, the translation between acoustic signals and motoric programs, may constitute a crucial mechanism for speech. During speech perception, the acoustic-motoric translations include the recruitment of cortical areas for the representation of speech articulatory features, such as place of articulation. Selective attention can shape the processing and performance of speech perception tasks. Whether and where sensorimotor integration takes place during attentive speech perception remains to be explored. Here, we investigate articulatory feature representations of spoken consonant-vowel (CV) syllables during two distinct tasks. Fourteen healthy humans attended to either the vowel or the consonant within a syllable in separate delayed-match-to-sample tasks. Single-trial fMRI blood oxygenation level-dependent (BOLD) responses from perception periods were analyzed using multivariate pattern classification and a searchlight approach to reveal neural activation patterns sensitive to the processing of place of articulation (i.e., bilabial/labiodental vs. alveolar). To isolate place of articulation representation from acoustic covariation, we applied a cross-decoding (generalization) procedure across distinct features of manner of articulation (i.e., stop, fricative, and nasal). We found evidence for the representation of place of articulation across tasks and in both tasks separately: for attention to vowels, generalization maps included bilateral clusters of superior and posterior temporal, insular, and frontal regions; for attention to consonants, generalization maps encompassed clusters in temporoparietal, insular, and frontal regions within the right hemisphere only. Our results specify the cortical representation of place of articulation features generalized across manner of articulation during attentive syllable perception, thus supporting sensorimotor integration during attentive speech perception and demonstrating the value of generalization.

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.

Thalamic Deep Brain Stimulation for Refractory Tourette Syndrome: Clinical Evidence for Increasing Disbalance of Therapeutic Effects and Side Effects at Long-Term Follow-Up.

OBJECTIVE: Thalamic deep brain stimulation (DBS) is effective in reducing tics in patients with refractory Tourette syndrome at the short-term. Here, we report on the long-term outcome. MATERIALS AND METHODS: Seven patients underwent bilateral DBS between 2001 and 2008. The target was the centromedian nucleus, substantia periventricularis and nucleus ventro-oralis internus cross point of the thalamus. The effect on tics and side effects were evaluated with a variable follow-up duration of 12 to 78 months. RESULTS: Patient 1 and 2 showed good tic improvements of 81.6% (60 months) and 50% (36 months), respectively. However, side effects like reducing levels of energy and visual disturbances increased. In patient 1, the target was changed to the anterior part of the internal pallidum and patient 2 switched the stimulator permanently off. Patient 3 experiences still satisfying results with a tic improvement of 88.9% (78 months). Patient 4 and 7 showed minor tic improvements of 34% (16 months) and 9% (60 months), respectively. In both patients side effects became more severe and the target was changed to the anterior part of the internal pallidum. Patient 5 showed a tic improvement of 27.5% (12 months) and went abroad for stimulation of the external globus pallidus. Patient 6 developed cerebellar atrophy. He experienced several nonstimulation related side effects and turned the stimulator off. CONCLUSIONS: There seems to be an increasing disbalance of therapeutic effects and side effects at long-term follow-up, often leading to either switching the stimulator off or new surgery with a different neuro-anatomic target.

Anterior Transthoracic Surgery with Motor Evoked Potential Monitoring for High-Risk Thoracic Disc Herniations: Technique and Results.

OBJECTIVE: To present our experience with anterior transthoracic surgery for high-risk thoracic disc herniations (TDHs) using motor evoked potential monitoring (MEPm). METHODS: We estimated surgical risk based on clinical and radiologic characteristics, including anteroposterior (AP) spinal canal occupation (SCO), AP spinal cord compression (SCC), residual AP spinal cord diameter (RSCD), and intramedullary signal changes (ISC). We analyzed Anand, ASIA, and Nurick scores, anesthesiologic, neurophysiological, and surgical reports. We considered >50% MEP signal deterioration significant. RESULTS: Out of 435 anterior transthoracic procedures, 77 concerned high-risk TDH(s): 69 single-level, 8 multilevel, 61 with clinical myelopathy, 6 with merely ISC. Mean SCO and SCC were 55.4% and 54.0% for single-level, 31.8% and 33.9% for multilevel cases. ISC were present in 64% of single-level and 50% of multilevel cases, calcifications in 87% of single-level and 84% of multilevel TDHs. We initially performed 23 mini-transthoracic approaches (mini-TTAs) and 24 thoracoscopic microdiscectomies (TMDs), more recently 29 TMDs (23 giant TDHs) and 1 transaxillary mini-TTA. Overall, 72 patients had reliable MEP signals. Isolated lower extremity MEP signal deteriorations (n = 21) correlated with maximal TDH AP diameter, SCO, SCC, and ISC. ASIA and Nurick scores improved in 45% and 66% respectively. One patient became paraplegic. MEP signal deterioration had 100% sensitivity, 75% specificity, and 19% positive predictive value during and 44% at the end of surgery. CONCLUSIONS: Maximal TDH AP diameter, SCO, SCC, (sub)total calcification, and ISC correlate with lower extremity MEP signal deterioration. In experienced hands, TMD with MEPm support is a safe, efficient procedure for high-risk TDHs.

Tonic and phasic changes in anteromedial globus pallidus activity in Tourette syndrome.

BACKGROUND: Tourette syndrome is a hyperkinetic neurodevelopmental disorder characterized by tics. OBJECTIVE: Assess the neuronal changes in the associative/limbic GP associated with Tourette syndrome. METHODS: Neurophysiological recordings were performed from the anterior (associative/limbic) GPe and GPi of 8 awake patients during DBS electrode implantation surgeries. RESULTS: The baseline firing rate of the neurons was low in a state-dependent manner in both segments of the GP. Tic-dependent transient rate changes were found in the activity of individual neurons of both segments around the time of the tic. Neither oscillatory activity of individual neurons nor correlations in their interactions were observed. CONCLUSIONS: The results demonstrate the involvement of the associative/limbic pathway in the underlying pathophysiology of Tourette syndrome and point to tonic and phasic modulations of basal ganglia output as a key mechanisms underlying the abnormal state of the disorder and the expression of individual tics, respectively. © 2017 International Parkinson and Movement Disorder Society.

Hinge-deleted IgG4 blocker therapy for acetylcholine receptor myasthenia gravis in rhesus monkeys.

Autoantibodies against ion channels are the cause of numerous neurologic autoimmune disorders. Frequently, such pathogenic autoantibodies have a restricted epitope-specificity. In such cases, competing antibody formats devoid of pathogenic effector functions (blocker antibodies) have the potential to treat disease by displacing autoantibodies from their target. Here, we have used a model of the neuromuscular autoimmune disease myasthenia gravis in rhesus monkeys (Macaca mulatta) to test the therapeutic potential of a new blocker antibody: MG was induced by passive transfer of pathogenic acetylcholine receptor-specific monoclonal antibody IgG1-637. The effect of the blocker antibody (IgG4Δhinge-637, the hinge-deleted IgG4 version of IgG1-637) was assessed using decrement measurements and single-fiber electromyography. Three daily doses of 1.7 mg/kg IgG1-637 (cumulative dose 5 mg/kg) induced impairment of neuromuscular transmission, as demonstrated by significantly increased jitter, synaptic transmission failures (blockings) and a decrease in the amplitude of the compound muscle action potentials during repeated stimulations (decrement), without showing overt symptoms of muscle weakness. Treatment with three daily doses of 10 mg/kg IgG4Δhinge-637 significantly reduced the IgG1-637-induced increase in jitter, blockings and decrement. Together, these results represent proof-of principle data for therapy of acetylcholine receptor-myasthenia gravis with a monovalent antibody format that blocks binding of pathogenic autoantibodies.

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.