Nora F. Dengler

Recording, analysis, and interpretation of spreading depolarizations in neurointensive care: Review and recommendations of the COSBID research group

Spreading depolarizations (SD) are waves of abrupt, near-complete breakdown of neuronal transmembrane ion gradients, are the largest possible pathophysiologic disruption of viable cerebral gray matter, and are a crucial mechanism of lesion development. Spreading depolarizations are increasingly recorded during multimodal neuromonitoring in neurocritical care as a causal biomarker providing a diagnostic summary measure of metabolic failure and excitotoxic injury. Focal ischemia causes spreading depolarization within minutes. Further spreading depolarizations arise for hours to days due to energy supply-demand mismatch in viable tissue. Spreading depolarizations exacerbate neuronal injury through prolonged ionic breakdown and spreading depolarization-related hypoperfusion (spreading ischemia). Local duration of the depolarization indicates local tissue energy status and risk of injury. Regional electrocorticographic monitoring affords even remote detection of injury because spreading depolarizations propagate widely from ischemic or metabolically stressed zones; characteristic patterns, including temporal clusters of spreading depolarizations and persistent depression of spontaneous cortical activity, can be recognized and quantified. Here, we describe the experimental basis for interpreting these patterns and illustrate their translation to human disease. We further provide consensus recommendations for electrocorticographic methods to record, classify, and score spreading depolarizations and associated spreading depressions. These methods offer distinct advantages over other neuromonitoring modalities and allow for future refinement through less invasive and more automated approaches.

Oxygen availability and spreading depolarizations provide complementary prognostic information in neuromonitoring of aneurysmal subarachnoid hemorrhage patients

Multimodal neuromonitoring in neurocritical care increasingly includes electrocorticography to measure epileptic events and spreading depolarizations. Spreading depolarization causes spreading depression of activity (=isoelectricity) in electrically active tissue. If the depression is long-lasting, further spreading depolarizations occur in still isoelectric tissue where no activity can be suppressed. Such spreading depolarizations are termed isoelectric and are assumed to indicate energy compromise. However, experimental and clinical recordings suggest that long-lasting spreading depolarization-induced depression and isoelectric spreading depolarizations are often recorded outside of the actual ischemic zones, allowing the remote diagnosis of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Here, we analyzed simultaneous electrocorticography and tissue partial pressure of oxygen recording in 33 aneurysmal subarachnoid hemorrhage patients. Multiple regression showed that both peak total depression duration per recording day and mean baseline tissue partial pressure of oxygen were independent predictors of outcome. Moreover, tissue partial pressure of oxygen preceding spreading depolarization was similar and differences in tissue partial pressure of oxygen responses to spreading depolarization were only subtle between isoelectric spreading depolarizations and spreading depressions. This further supports that, similar to clustering of spreading depolarizations, long spreading depolarization-induced periods of isoelectricity are useful to detect energy compromise remotely, which is valuable because the exact location of future developing pathology is unknown at the time when the neurosurgeon implants recording devices.

Moyamoya Vessel Pathology Imaged by Ultra-High-Field Magnetic Resonance Imaging at 7.0 T

BACKGROUND Prompt diagnosis of vessel pathology and appropriate treatment of moyamoya vasculopathy (MMV) are essential to improve long-term prognosis. The aims of our study were to explore the diagnostic value of ultra-high-field (UHF) magnetic resonance imaging at 7.0 T in MMV patients and to compare the applicability of two different 7.0 T vessel imaging modalities to 3.0 T magnetic resonance angiography (MRA) and digital subtraction angiography (DSA). METHODS In a World Health Organization-registered and prospective imaging trial, patients were investigated at 7.0 T magnetization-prepared rapid-acquisition gradient echo (MPRAGE)-MRA and time-of-flight (TOF)-MRA, 3.0 T TOF-MRA, and by DSA. RESULTS Six patients were included in our study and evaluated for MMV. 3.0 T TOF-MRA and 7.0 T MPRAGE-MRA were able to depict the complete major vascular tree and confirmed MMV-specific steno-occlusions of major intracranial arteries, as previously identified by DSA. 7.0 T TOF-MRA was limited to visualization of the circle of Willis as well as the internal carotid artery only. Donor vessels for bypass surgery (i.e., branches of superficial temporal artery) could be sufficiently visualized with all magnetic resonance modalities. CONCLUSIONS Our results indicate that a specific 7.0 T vascular imaging protocol yields diagnostic information about vessel pathology in MMV that approximates conventional DSA. 7.0 T MPRAGE was superior to 7.0 T TOF-MRA due to shorter scanning times and better brain coverage. To date, however, limited availability of 7.0 T technology in medical facilities as well as technical and procedural constraints excludes a fair amount of patients from the clinical 7.0 T imaging process.

A novel score to predict shunt dependency after aneurysmal subarachnoid hemorrhage

OBJECTIVE Feasible clinical scores for predicting shunt-dependent hydrocephalus (SDHC) after aneurysmal subarachnoid hemorrhage (aSAH) are scarce. The chronic hydrocephalus ensuing from SAH score (CHESS) was introduced in 2015 and has a high predictive value for SDHC. Although this score is easy to calculate, several early clinical and radiological factors are required. The authors designed the retrospective analysis described here for external CHESS validation and determination of predictive values for the radiographic Barrow Neurological Institute (BNI) scoring system and a new simplified combined scoring system. METHODS Consecutive data of 314 patients with aSAH were retrospectively analyzed with respect to CHESS parameters and BNI score. A new score, the shunt dependency in aSAH (SDASH) score, was calculated from independent risk factors identified with multivariate analysis. RESULTS Two hundred twenty-five patients survived the initial phase after the hemorrhage, and 27.1% of these patients developed SDHC. The SDASH score was developed from results of multivariate analysis, which revealed acute hydrocephalus (aHP), a BNI score of ≥ 3, and a Hunt and Hess (HH) grade of ≥ 4 to be independent risk factors for SDHC (ORs 5.709 [aHP], 6.804 [BNI], and 4.122 [HH]; p < 0.001). All 3 SDHC scores tested (CHESS, BNI, and SDASH) reliably predicted chronic hydrocephalus (ORs 1.533 [CHESS], 2.021 [BNI], and 2.496 [SDASH]; p ≤ 0.001). Areas under the receiver operating curve (AUROC) for CHESS and SDASH were comparable (0.769 vs 0.785, respectively; p = 0.447), but the CHESS and SDASH scores were superior to the BNI grading system for predicting SDHC (BNI AUROC 0.649; p = 0.014 and 0.001, respectively). In contrast to CHESS and BNI scores, an increase in the SDASH score coincided with a monotonous increase in the risk of developing SDHC. CONCLUSIONS The newly developed SDASH score is a reliable tool for predicting SDHC. It contains fewer factors and is more intuitive than existing scores that were shown to predict SDHC. A prospective score evaluation is needed.

Prediction of cerebral infarction and patient outcome in aneurysmal subarachnoid hemorrhage: comparison of new and established radiographic, clinical and combined scores

There are numerous grading scales to describe the severity of aneurysmal subarachnoid hemorrhage (aSAH) and to predict outcome. Historically, outcome measures are heterogeneous and the comparability of grading scales is therefore limited. We designed this study to compare radiographic, clinical and combined grading systems in aSAH.

Large Size Hemicraniectomy Reduces Early Herniation in Malignant Middle Cerebral Artery Infarction

Background: Decompressive hemicraniectomy (DHC) reduces mortality and improves outcome after malignant middle cerebral artery infarction (MMI) but early in-hospital mortality remains high between 22 and 33%. Possibly, this circumstance is driven by cerebral herniation due to space-occupying brain swelling despite decompressive surgery. As the size of the removed bone flap may vary considerably between surgeons, a size too small could foster herniation. Here, we investigated the effect of the additional volume created by an extended DHC (eDHC) on early in-hospital mortality in patients suffering from MMI. Methods: We performed a retrospective single-center cohort study of 97 patients with MMI that were treated either with eDHC (n = 40) or standard DHC (sDHC; n = 57) between January 2006 and June 2012. The primary study end point was defined as in-hospital mortality due to transtentorial herniation. Results: In-hospital mortality due to transtentorial herniation was significantly lower after eDHC (0 vs. 11%; p = 0.04), which was paralleled by a significantly larger volume of the craniectomy (p < 0.001) and less cerebral swelling (eDHC 21% vs. sDHC 25%; p = 0.03). No statistically significant differences were found in surgical or non-surgical complications and postoperative intensive care treatment. Conclusion: Despite a more aggressive surgical approach, eDHC may reduce early in-hospital mortality and limit transtentorial herniation. Prospective studies are warranted to confirm our results and assess general safety of eDHC.

Mechanisms, Treatment, and Patient Outcome of Iatrogenic Injury to the Brachial Plexus–A Retrospective Single-Center Study

BACKGROUND Injury to the brachial plexus is a devastating condition, with severe impairment of upper extremity function resulting in distinct disability. There are no systematic reports on epidemiology, causative mechanisms, treatment strategies. or outcomes of iatrogenic brachial plexus injury (iBPI). METHODS We screened all cases of iatrogenic nerve injuries recorded between 2007 and 2017 at a single specialized institution. Mechanism of iBPI, type of previous causative intervention, location and type of the lesion as well as the type of revision surgery and functional patient outcome were analyzed. RESULTS We identified 14 cases of iBPI, which all presented with significant impairment of upper extremity motor function (at least 1 muscle Medical Research Council grade 0). Neuropathic pain was present in most patients (11/14). Orthopedic shoulder procedures such as rotator cuff fixation, arthroplasty, and repositioning of a clavicle fracture accounted for iBPI in 7 of 14 patients. Other reasons for iBPI were resection or biopsy of a peripheral nerve sheath tumor in 3 patients or lymph node situated at the cervicomediastinal area in 2 patients. Mechanisms also included transaxillary rib resection in one and sternotomy in another patient. The treatment of iBPI was conducted according to each individuals needs and included neurolysis in 4, nerve grafting in 9, and nerve transfers in 1 patient. We found improved symptoms after treatment in most patients (11/14). CONCLUSIONS Most common causes for iBPI were shoulder surgery and resection or biopsy of peripheral nerve sheath tumor and lymph nodes. Early referral to specialized peripheral nerve centers may help to improve functional patient outcome.

Brain Slices From Human Resected Tissues

Human brain slices permit not only functional characterization of neuronal and nonneuronal cells in the hippocampus and cortex of patients surgically treated for tumors or pharmacoresistant epilepsy, including developmental disorders. They allow for detection of spontaneous activities, related to in vivo recorded EEG potentials, and also testing of hypotheses regarding increased seizure susceptibility. Underlying mechanisms can be investigated by inducing abnormal “epileptiform” activity. The properties of induced epileptiform activity might be evaluated in relation to pharmacoresistance and pathological diagnosis of the patient. Comparison of new pharmacological agents to standard AEDs might be helpful for new therapies. In some cases, alternative therapies, such as local delivery of drugs or deep brain stimulation protocols, can be proven. Importantly, organotypic slice cultures are maintained in vitro for prolonged periods, permitting toxicological studies and evaluation of slowly acting drugs.

Standard-sampling microdialysis and spreading depolarizations in patients with malignant hemispheric stroke

Spreading depolarizations (SD) occur in high frequency in patients with malignant hemispheric stroke (MHS). Experimentally, SDs cause marked increases in glutamate and lactate, whereas glucose decreases. Here, we studied extracellular brain glutamate, glucose, lactate, pyruvate and the lactate/pyruvate ratio in relationship to SDs after MHS. We inserted two microdialysis probes in peri-infarct tissue at 5 and 15 mm to the infarct in close proximity to a subdural electrode strip. During 2356.6 monitoring hours, electrocorticography (ECoG) revealed 697 SDs in 16 of 18 patients. Ninety-nine SDs in electrically active tissue (spreading depressions, SDd) were single (SDds) and 485 clustered (SDdc), whereas 10 SDs with at least one electrode in electrically inactive tissue (isoelectric SDs, SDi) were single (SDis) and 103 clustered (SDic). More SDs and a significant number of clustered SDs occurred during the first 36 h post-surgery when glutamate was significantly elevated (> 100 µM). In a grouped analysis, we observed minor glutamate elevations with more than two SDs per hour. Glucose slightly decreased during SDic at 5 mm from the infarct. Directions of SD-related metabolic changes correspond to the experimental setting but the long sampling time of standard microdialysis precludes a more adequate account of the dynamics revealed by ECoG.

Super-selective cervical nerve root stimulation in contralateral C7 transfer: An intraoperative study

OBJECTIVE We designed this study using super-selective intraoperative cervical nerve root stimulation aiming to support decision making about complete or partial contralateral C7 (cC7) nerve root transfer in patients with multiple cervical root avulsion injury. METHODS Super-selective intraoperative stimulations of anterior, lateral, medial and posterior aspect of C5-C8 nerve roots were performed. Compound muscle action potentials (CMAP) were recorded in the lateral part of the deltoid (DM), long head of biceps brachii (BCM), brachioradial (BRM), long head of triceps brachii (TCM), and extensor digitorum communis (EDC) muscle. Muscle strength was documented immediately after cC7 transfer procedures and on scheduled follow-up visits according to the Medical Research Council (MRC) scale. RESULTS In the DM, stimulation of the posterior aspect of C5 resulted in the largest CMAP amplitudes (2.0 mV ± 1.9; 80% ± 28.3). The BCM CMAPs induced by the different aspects of C6 all revealed homogenous stimulation results. Stimulation of the lateral aspect of C7 induced the largest amplitude of TCM CMAPs (1.3 mV ± 1.0; 67.1% ± 43.3). CMAP amplitudes of individual muscles and individual contributions of cervical nerve roots to the TCM varied between subjects. Overall donor side morbidity was low, no permanent motor deficit occurred. CONCLUSION A super-selective intraoperative cervical nerve root stimulation may help minimize donor side morbidity in transfer procedures. Individual differences of cervical nerve root innervation pattern need to be addressed in future electrophysiological studies. SIGNIFICANCE Our study outlines individual differences of cervical nerve root innervation pattern.