Arbeitstagung Neurointensivmedizin 41. Jahrestagung der DGNI und DSG

Professor

Dr. rer. hum. biol.

Prof. Dr.

PD Dr. Dipl.-Psych.

Delirium in acute stroke – Does single-channel EEG help us in clinical practice?

Bewusstseinsstörungen

Notfall- und Intensivtherapie des schweren Hirninfarkts

Abstract-Text (inkl. Referenzen und Bildunterschriften) Background: About 10 percent of patients suffering from an acute stroke get diagnosed with delirium during the associated hospital stay, with older age increasing the risk (Dahl et al. 2010). It is well known that generalized slowing in the electroencephalogram (EEG) supports the diagnosis of delirium (Jacobson &amp; Jerrier, 2000). In this context, we examine the potential of a single-channel EEG as an easy-to-use device on stroke units. Comparison of bihemispheric EEG recordings with a right fronto-parietal EEG channel (DeltaScan®) will be analyzed in context with the clinically established delirium diagnosis. Methods: Within the first five days after stroke onset, in 9 of 63 patients (25-90 years) a delirium was diagnosed according to DSM-V criteria. All patients received DeltaScan® and a 21 channel EEG recording (200 Hz, avg. reference, impedances ≤ 10 kΩ). Based on 2-minute eyes-closed resting state segments we analyzed power spectral density (PSD) in predefined frequency bands (delta 1-4 Hz, theta 4-8 Hz, alpha 8-12 Hz, beta 15-30 Hz). Analyses were conducted in MNE (v1.3.1), Python (3.10) and RStudio (v4.2.1). Results: We found patients with right hemispheric stroke having a higher probability to be false positive in DeltaScan® (p=0.01, OR=5.90). EEG based power analysis revealed frontal delta (sensitivity 0.82, CI=0.57-0.97) and left hemispheric frontal theta power (sensitivity 0.86, CI=0.67-0.98) as the best predictors of diagnosed delirium. Conclusion: When EEG is used in clinical practice to support a delirium diagnosis, bihemispheric recordings should be preferred over unilateral recordings in stroke patients. Slowing in the delta- or theta-frequency spectrum over the site of stroke can lead to false-positive results in single channel EEG based delirium scoring. Emphasis should be given to frontal electrodes of both sides. Dahl et al. 2010. doi: 10.1111/j.1600-0404.2010.01374.x. PMID: 20586734. Jacobson &amp; Jerrier, 2000. doi: 10.153/SCNP00500086. PMID: 10837097.

ePoster

Diagnostic adjudication of chronic inflammatory demyelinating polyneuropathy in the ADHERE trial – Updates on the first 200 cases

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Abstract-Text (inkl. Referenzen und Bildunterschriften) Introduction: Accurate diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) can be challenging due to heterogeneous clinical presentation, relying heavily on electrodiagnostic acumen. EFNS/PNS 2010 criteria have been used to guide trial enrollment. Objective: We previously reported on how a CIDP Confirmation Committee (CCC) verified accurate diagnosis for the first 100 cases enrolled in the ADHERE trial investigating efgartigimod alfa. This update covers the first 200 cases. Methods: Nine neurologists with extensive experience in treating and researching CIDP comprise the CCC. They reviewed 200 de-identified cases via an electronic adjudication system. A patient was eligible for enrollment if 2 experts independently confirmed diagnosis as definite/probable CIDP. When diagnoses were discordant (eg, definite/probable vs possible/nonCIDP), the CCC chair provided the final decision. Results: Of these 200 patients, 83 were ineligible (possible/nonCIDP [n=76], unknown [n=7]). NonCIDP (n=66) included various neuropathies (n=33), Guillain-Barré Syndrome (n=4), other diagnoses (n=10), and no alternative or discrepant diagnoses (n=19). The CCC confirmed definite/probable CIDP in 117 patients; of these, 78.6% (92/117) had typical CIDP, 17.9% (21/117) had atypical CIDP, and 3.4% (4/117) met criteria without meeting specific phenotype. Rate of concordance among experts was higher for typical (66.7% [66/99]) than atypical CIDP (37.5% [9/24]), and higher for definite/probable CIDP (76.0% [79/104]) than possible /nonCIDP (24% [25/104]). Conclusion: Diagnosing CIDP is difficult, particularly in complex cases where the diagnosis may not fulfill the CIDP criteria. Accordingly, discordant CCC diagnoses occurred more frequently in complex cases. Having the CCC to verify accurate CIDP diagnoses in ADHERE may serve as a model for future CIDP trials.

Prof. Dr. med.

Dr. med.

The relevance of variable positive end-expiratory pressure and inspiration pressure settings on intracranial pressure in mechanically ventilated neurocritical care patients

Translationale Neuro-Intensivmedizin

Abstract-Text (inkl. Referenzen und Bildunterschriften) Background. In mechanically ventilated neurocritical care patients positive end-expiratory pressure (PEEP) has long been discussed as potentially detrimental for intracranial pressure (ICP). However, various studies failed to identify a relevant effect of PEEP on ICP and to date optimal ventilation strategy concerning airway pressure in brain-injured patients are not established. In this prospective physiological study, we focused on the relevance of different ventilation pressure settings on ICP. Methods. We prospectively included 22 adult, intubated and mechanically ventilated neurocritical care patients with intraventricular ICP monitoring. Patients were only included with a stable ICP &lt; 20mmHg over at least 72 hours and absence of acute lung injury such as pneumonia or adult respiratory distress syndrome (ARDS). Each patient passed three measurement cycles: at first (cycle 1; C1), PEEP and inspiration pressure (Pinsp) were increased simultaneously, second (C2), only PEEP was increased and third (C3), only Pinsp was increased. The pressure settings were continuously increased in steps of 2 mbar every 5 minutes starting at baseline (t0) until a maximum of +12 mbar (t12) was reached. We adjusted the ventilation to accomplish stable endtidal carbondioxide (etCO2) levels. ICP and hemodynamic Parameters at each ventilator setting were recorded. The local ethic committee approved the study under reference #5162R. Results. In the C1 group, while increasing PEEP (from 6mbar at t0 to 18mbar at t12) and Pinsp (from 17mbar at t0 to 30mbar at t12), we recorded a continuous increase in ICP (5mmHg at t0 to 10mmHg at t12). In the C3 group with a non-dynamic PEEP fixed at median 6 mbar (range 5-10 mbar) and only gradual increase in Pinsp from (t0) 17 to (t12) we saw a stable ICP of median 4 mmHg (range 0 – 11mmHg). The difference in ICP for t0 and t2 was not significant, however with increasing difference in PEEP the difference in ICP became increasingly significant (t4 p=0.025; t6 p=0.024; t8, t10 and t12 p=0.003 respectively). Conclusion. In this setting, a dynamically increased PEEP with increasing Pinsp increases ICP values as compared to fixed PEEP setting with increasing Pinsp.

Temporal course of secondary transfer of neurosurgical intensive care patients

Abstract-Text (inkl. Referenzen und Bildunterschriften) Objective: Patients with acute cerebral or spinal pathologies require treatment in a specialized neurocenter. These life-threatening conditions are often diagnosed in tertiary-care hospitals without an appropriate neurosurgical and neurointensive care. Therefore an urgent transfer to a neurocenter is mandatory to ensure the timely begin of necessary surgical and/or neurointensive interventions. The organization and execution of secondary transfers require interdisciplinary cooperation and are influenced by many external factors, which may lead to disastrous delays in patient transfer. In this study, we examine this process for possible influencing factors. Methods: This is an ongoing prospective observational study including all patient with life-threatening cerebral or spinal conditions presented to our department from tertiary-care hospitals. We recorded the time point of peripheral patient admittance and the periods until diagnosis was established, the patient was presented to our department, transfer was organized and conducted and the patient finally arrived in our department. Epidemiological patient data in addition to data provided by the emergency medical services (EMS) and the tertiary-care hospitals were collected in a standardized questionnaire. Results: So far, 34 patients (mean age 62.6±13.1 years, 56% female) have been included with complete data sets. Most tertiary hospitals were within 30 km distance (52%). Time between confirmed neurological emergency and contact with our department was 41±42 minutes and time until arrival of EMS to pick up the patient in the tertiary hospital was 28±30 minutes. The actual transfer took 23±9 minutes and positively correlated with the distance (p&lt;0.001). Overall time between CT and arrival in our department was 104±38 minutes and did not correlate with diagnosis (p=0.449), initial Glasgow coma scale (p=0.957) or patient age (p=0.059) but correlated significantly with time of day (p&lt;0.001) with longer intervals during working hours as compared to nights (114 vs 92 minutes). Conclusion: Our preliminary analysis shows that relevant time passes before diagnostic measures are performed and the transfer is organized. During working hours a significant delay occurs potentially due to the work load in tertiary hospitals. Our analysis underlines the necessity of establishing a network and training non-neurosurgical personnel in tertiary hospitals to improve awareness and shorten transfer times.

Automating intracranial pressure transducer position identification

Abstract-Text (inkl. Referenzen und Bildunterschriften) OBJECTIVE: The position of an external ventricular drain (EVD) stopcock transducer is a determinant of the accuracy of intracranial pressure (ICP). This study validates the feasibility of a stopcock position sensor (SPS) and annotation hub to provide continuous data acquisition (CDA) for accurate ICP data. BACKGROUND: The impact of environmental and contextual factors on physiological data such as ICP is well known. For example, when the stopcock is in the open-to-drain position, the ICP reading is neither reliable nor accurate. In patients with acute acquired brain injury this data is often recorded manually. Automating the capture of contextual data will improve the quality of the data for post hoc analysis including machine learning. With respect to ICP, identifying the invalid segments of data where the stopcock is positioned to &quot;drain CSF&quot; vs &quot;monitor ICP&quot; is essential. METHODS: We created an SPS that collects contextual data and generates time-synchronized annotations linked to physiologic data. In a prospective observational trial we evaluate the efficacy of an SPS to accurately identify when a transducer is open to drain vs monitoring ICP. After consent, eligible subjects with an EVD in situ were monitored for up to 24 hours using the SPS. RESULTS: Phase 1 and 2 prototypes of the SPS were evaluated between January 2022 and April 2023. Between April 2023 and September 2023 the SPS was placed on 12 patients in the Neuroscience Intensive Care Unit. Patients were admitted for subarachnoid hemorrhage (5), intraventricular hemorrhage (2), mass lesion (4), and congenital Hydrocephalus (1). All patients completed the trial and provided linked readings to ICP data and there have been zero adverse events or complications during the study. CONCLUSIONS: Automated CDA is feasible in the NSICU for patients with acute brain injury. The use of annotated CDA data will enhance the clinical utility of ICP monitoring by providing higher accuracy and reliability of ICP readings. Additional phases of this study hope to further validate initial findings.

Intracranial pressure monitoring is affected by transducer blood contamination

Abstract-Text (inkl. Referenzen und Bildunterschriften) Funding: Helene Fuld Health Trust National Institute for Evidence-Based Practice in Nursing and Healthcare Research Grant. Natus Medical Inc. donated equipment. Background. Acquired brain injury patients may have placement of an external ventricular drain (EVD) to manage elevated intracranial pressure (ICP). Successful ICP management requires accurate monitoring and reporting of ICP via a pressure transducer. This study examines the impact on ICP accuracy when a transducer is contaminated by solutions of varying viscosity. Methods. This preclinical laboratory comparative design study used an acrylic pressure chamber filled with 6,000mL of saline to simulate a human skull model. Two Edwards TruWave strain gauge transducers (arbitrarily selected as control (CONT) and Experiment (EXP)) were attached to 2 EVD drainage systems and connected to the chamber via EVDs (Natus). After priming both transducers with saline, they were leveled to the center of the chamber and zero calibrated. To simulate changes in ICP, the chamber was moved to 6 different elevations (Figure 1). At each position, 4 metrics were recorded: time until each transducer 1st reached the expected pressure; time until the pressure stabilized for 30 seconds; pressure 1 minute after the position change; and final resting pressure. Eight study conditions include: (1) priming of both transducers with saline; (2-6) priming only the EXP transducer with a 10, 25, 50, 75, 100% glycerol:saline solution; (7) the EXP transducer was re-zeroed when primed with 100% glycerol; (8) primed the EXP transducer with human blood. Data was continually acquired via Natus CNS (formerly Moberg) at 256 Hz. Results. Wilcoxon signed rank test models reveal statistically significant differences for CONT vs EXP in median: (1) time to first reach expected pressure (9.5 [5.5-14.5.0] vs 18.0 [11.0-27.0] sec; P&lt;.0001); (2) time to stability (9.5 [5.5-17.0] vs 23.0 [14.0-32.0] sec; P&lt;.0001); (3) pressure at 1-minute (11.0 [8.5-28.5] vs 9.0 [8.0-27.0] mmHg; P&lt;.0001); and (4) final resting pressure (11.0 [9.0-29.0] vs 9.0 [8.0-27.0] mmHg; P&lt;.0001). Conclusion. High viscosity contaminates (e.g., blood) in the transducer impact the time between transient changes and stable measurement in ICP monitoring. Contaminate in the transducer results in a longer time for ICP values to stabilize and the resulting pressure is significantly lower than the expected pressure. Future study iterations should explore the long-term effects of transducer contamination on the validity of pressure values and the time necessary for a measurement to stabilize following a transient (e.g., opening EVD).

Analyzing door-to-groin times for endovascular thrombectomy – Tenecteplase vs. Alteplase in acute ischemic stroke treatment

Abstract-Text (inkl. Referenzen und Bildunterschriften) Introduction: Acute ischemic stroke (AIS) outcomes are time-sensitive. Reducing door-to-groin (DTG) times is critical for improving patient outcomes for eligible patients admitted with AIS. Tenecteplase (TNK) has emerged as a potential alternative to alteplase (ALT) in AIS and may expedite DTG times. TNK offers advantages such as simplified administration, reduced risk of dosage errors, and suitability for a "give and go" protocol, facilitating faster patient transfer to higher stroke centers. This study compares TNK and ALT DTG times. Methods: Data from the Lone Star Stroke Consortium (LSSC) registry, encompassing 9 Texas hospitals were analyzed. The dataset mapped subject data to Get-With-the-Guidelines (GWTG) stroke variables and included AIS patients who received either ALT or TNK between October 2019 and March 2023. Patient data were categorized into ALT or TNK groups. Descriptive statistics and measures of central tendency were first examined. Models were constructed using the Wilcoxon signed-rank test to explore median differences in DTG times by group assignment. Results: Of 621 patients in the study, 459 received ALT, and 162 received TNK. Among these, 142 patients (90 ALT and 52 TNK) that presented directly to the treating center underwent endovascular thrombectomy (EVT); transfer subjects were excluded. The groups had similar mean age (69.2 [14.7]) and NIHSS scores (11.1 [7.5]; P&gt;.05). The median DTG times were 113 min (91.5-132.8) for ALT versus 93 min (69-109.8) for TNK (Wilcoxon signed-rank Z = -2.52; P&lt; .05). Conclusion: TNK demonstrated superiority in reducing DTG times when compared to ALT in the treatment of eligible patients admitted with AIS. These findings suggest that TNK may lead to earlier interventions for large vessel occlusions and subsequently improve patient outcomes. Statistically significant difference is found between TNK and ALK, and the use of TNK reduces the DTG time in our study sample. This study highlights the potential benefits of adopting TNK as a thrombolytic agent in AIS treatment protocols.

Long-term safety, tolerability, and efficacy of subcutaneous Efgartigimod PH20 in patients with generalized Myasthenia Gravis – Interim results of the ADAPT-SC+ study

Abstract-Text (inkl. Referenzen und Bildunterschriften) Introduction: In ADAPT-SC, subcutaneous (SC) efgartigimod PH20 (coformulated with recombinant human hyaluronidase PH20) 1000 mg was shown to have noninferior total IgG reduction to efgartigimod IV 10 mg/kg (approved in US, Japan, and EU) resulting in similar clinical improvement in patients with generalized myasthenia gravis (gMG). Patients completing ADAPT-SC, or enrolled in ADAPT+, were eligible to participate in the ongoing open-label extension, ADAPT-SC+. Objective: To evaluate long-term safety, tolerability, and efficacy of efgartigimod PH20 SC in patients with gMG enrolled in the ADAPT-SC+ open-label extension study. Methods: Efgartigimod PH20 SC 1000mg was administered in cycles of 4-weekly injections. Subsequent cycles were initiated at least 28 days from the last dose based on clinical evaluation. Clinical efficacy was assessed utilizing the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale. Results: As of March 2022, 164 participants received ≥1 dose of efgartigimod PH20 SC. Patients received ~3 cycles over a mean (SD) study duration of 170 (59) days, resulting in 72 patient-years of observation. Adverse events (AEs) were predominantly mild/moderate. The most frequent AEs were injection site erythema (25.6%), headache (15.2%), and COVID-19 (11.6%). All injection site reactions (ISRs) were mild/moderate and did not lead to treatment discontinuation. ISRs typically occurred within 24 hours of administration, resolved spontaneously, and incidence decreased with subsequent cycles. Two deaths were reported (metastatic renal cancer and COVID-19); neither were deemed efgartigimod-related per investigator. Improvement from cycle baseline in MG-ADL total score (mean [SE] improvement at week 4: –4.0 [0.25]) was observed in cycle 1, with consistent and repeatable improvements seen in subsequent cycles. Long-term treatment with efgartigimod PH20 SC 1000 mg reduced disease severity, as assessed by the MG-ADL scale, and improved the quality of life of patients with gMG. Speed of onset, magnitude, and repeatability of improvements in MG-ADL were similar to those with efgartigimod IV during ADAPT/ADAPT+. Conclusion: Results suggest multiple cycles of efgartigimod PH20 SC were well tolerated, with no safety concerns identified compared to ADAPT-SC. Treatment with efgartigimod PH20 SC led to consistent and repeatable reductions in MG-ADL total score, and the observed efficacy profile was consistent with ADAPT/ADAPT+.

High frequency oscillations may improve somatosensory evoked potential detection of good outcomes in cardiac arrest survivors

Neurologische Notfallmedizin

Abstract-Text (inkl. Referenzen und Bildunterschriften) Background: Somatosensory evoked potentials (SEPs) are widely considered the most specific predictor of poor prognosis in coma when cortical responses are absent, but are nonspecific for a good prognosis when present. High-frequency oscillations (HFOs) within the SEP waveform appear to predict neurologic recovery in animal models, but are difficult to measure in an electrically complex clinical environment. In a retrospective study of patients with neurologic injury resulting in coma, we sought to develop a measure of HFOs from clinical diagnostic SEPs and determine if the addition of this measure improved the predictive value of a normal SEP result. Materials and Methods: We identified all adult patients (N=58) who underwent diagnostic SEPs from 2020-2022 at the Johns Hopkins Hospital for prognostication in coma, including all etiologies of coma. To capture short-term neurologic changes, the primary outcome measure was the final in-hospital Glasgow Coma Scale (GCS). Using SEP waveform data from only the patients with bilaterally present N20s, we developed a measure of HFO power using the normal time-frequency space (NTFS) and subsequent evoked-to-spontaneous ratios (ESRs) to account for background noise, with the median value for binary classification. We additionally trained a support vector machine (SVM) model on the HFO-ESRs as a secondary predictive model. Results: The mean age was 55 (+/-17) years, 31% female. Primary injuries resulting in coma were post-cardiac arrest hypoxic-ischemic (56%), primary respiratory hypoxia (18%), intracranial hemorrhage (12%), hypotension (6%), traumatic brain injury (3%), and other etiologies (6%). 34 patients had bilaterally present N20s; of these, 14 had final GCS&gt;=9, and 20 had final GCS&lt;=8, with 17 patients above and below median HFO-ESR. In those patients with N20s, the addition of averaged HFO-ESRs greater than the median value predicted final GCS&gt;=9 with 55% specificity. Use of the SVM model further improved specificity to 65%. Conclusions: In this novel investigation of SEP-HFOs in multiple etiologies of coma, we developed a new measure of HFOs detectable in the electrically complex ICU environment. Incorporation of this measure in patients with positive N20s may improve the specificity of the SEP to predict in-hospital GCS outcomes, although this would require further exploration and validation in larger prospective studies.

Disclosures
This work was supported by the U.S. Assistant Secretary of Defense for Health Affairs, through the Defense Medical Research and Development Program / Joint Program Committee 6 / Combat Casualty Care Research Program / Precision Trauma Care Research Award under Award No. W81XWH-19-2-0013. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the U.S. Department of Defense.

A gap analysis of common data elements for machine learning in neurocritical care

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Abstract-Text (inkl. Referenzen und Bildunterschriften) Background Common Data Elements (CDEs) were developed to harmonize data sets in clinical trials. Although they are successful in harmonizing multi-study data, they fall short in providing relevant annotations for machine learning algorithms in research applications and routine clinical care. Our focus in this study was to identify the gaps in harmonization of multimodal physiological data from neurocritical care (NCC) patients. Methods With prior work in data harmonization, nomenclature standards, and a small group of stakeholders, we performed a gap analysis between CDEs and terms needed to characterize data acquisition and data analysis. We reviewed National Institute of Neurological Disorders and Stroke (NINDS) CDE terms for traumatic brain injury from 18 modalities across nine measurement categories. After tabulating the CDEs, we separated them based on if they were related to data acquisition (e.g. intracranial pressure device type, C01572) or data analysis (e.g. intracranial pressure mean daily measurement, C01575). We cross-referenced each CDE set with monitoring scenarios and existing standard care guidelines to determine additional terms needed to correctly characterize the acquisition and analysis of the data. We then performed a second gap analysis with the Brain Trauma Foundation updated CDEs for physiology and big data with 21 modalities across the same nine measurement categories. Results After conducting our gap analysis, we observed that 21 modalities lacked critically important terms with respect to CDEs to describe data acquisition and analysis. We found that for 20 modalities, additional data acquisition terms were necessary to improve standardization of data across institutions. We also identified and added terms to 20 modalities for data analysis. EEG was the only modality considered adequately contextualized in the original CDE database. Other analysis terms were omitted for being too study specific. For example, "intracranial pressure (ICP) episode greater 20 mmHg count" (CDE C01577) was removed as standards of care have changed (ICP &gt; 20 vs ICP &gt; 22). Conclusion Although studies supported by the NINDS adopt CDEs, they fall short when applied to annotating data in routine NCC and studies requiring rigorous analysis of monitored data. Our work will be valuable in extending concepts and use of CDEs to routine care.

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