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Background and Purpose: In 1916, Hans H. G. Queckenstedt (1876-1918) was the first to describe a test aimed at detecting spinal cerebrospinal fluid (CSF) space obstruction through lumbar CSF pressure measurements in paraplegic patients. For this test, bilateral jugular vein compression was applied during lumbar puncture and consecutive changes in lumbar CSF pressure were then observed. Findings were rated as normal, or indicative of incomplete or complete spinal block. This test, known as Queckenstedt's test, became widely adopted and further developed in the field., Methods: This systematic literature review provides an overview of the milestones in research using Queckenstedt's test., Results: Clinical research involving Queckenstedt's test was widely disseminated across the globe. In 1922, the proof of concept for Queckenstedt's test was provided by James B. Ayer (1882-1963) through simultaneous cisternal and lumbar CSF pressure measurements. He found that the cisternal (in contrast to lumbar) pressure remained responsive in cases with spinal block. The test was further refined up until the 1960s, and was considered a routine diagnostic procedure for testing of spinal canal obstruction. Developments in non-invasive spinal computed tomography and magnetic resonance imaging led to a significant decline in interest in Queckenstedt's test, and the test eventually disappeared from textbooks and clinical routine. However, at the beginning of the 21st century there was renewed interest in revealing the biomechanical properties of the CSF through advanced recording and computational techniques to complement spinal imaging., Conclusion: Spine and spinal cord physicians should be familiar with Queckenstedt's test, which not only represented a milestone in spinal diagnostics, but provided a physiological framework for the appreciation of spinal cord compression that is still valid today., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objective: Degenerative cervical myelopathy (DCM) is a centromedullary spinal cord disorder mainly affecting crossing fibers. While contact heat evoked potentials (CHEPs) are sensitive in detecting DCM by testing spinothalamic integrity, somatosensory evoked potentials (dSSEPs) show unaffected dorsal column conduction. Intra-epidermal electrically evoked potentials (IEEPs) have unknown spinal propagation after noxious stimulation. We investigated (1) the spinothalamic tract propagation and (2) the discriminative power in detecting spinal pathology of IEEPs compared to CHEPs and dSSEPs in DCM., Methods: DCM was diagnosed by neurological examination regarding stenosis (MRI). Stimulation of C6, C8, and T4 dermatomes yielded dSSEPs, CHEPs, and IEEPs. (1) Spinal propagation was assessed through concordant or discordant responses, and (2) discriminative power was determined using receiver operating characteristic curves (ROC)., Results: Twenty-seven patients (8F, 56 ± 12yrs) with DCM were analyzed and compared to age-matched healthy controls. IEEPs were abnormal in 43-54%, CHEPs in 37-69%, and dSSEPs in 4-12%. IEEPs showed high concordance with abnormalities of CHEPs (62-69%). ROC analyses showed good discriminative power of CHEPs and IEEPs contrary to dSSEPs., Conclusions: The concordance of abnormal responses of CHEPs and IEEPs contrary to dSSEPs suggests spinothalamic propagation of IEEPs., Significance: Minimal differences between CHEPs and IEEPs suggest complementary potential by the combined testing of spinothalamic tract integrity., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Timely and sufficient decompression are critical objectives in degenerative cervical myelopathy (DCM) and spinal cord injury (SCI). We previously investigated intraoperative cerebrospinal fluid pressure (CSFP) for determining surgical outcomes. However, confounding factors during the intra- and postoperative setting need consideration. These are related to type of respiration (i.e., artificial vs. natural) and anesthesia, which affect CSFP dynamics through the interaction between the cardiorespiratory system and the CSF compartment. This retrospective cohort study (NCT02170155) aims to systematically investigate these factors to facilitate CSFP interpretation. CSFP was continuously measured through a lumbar catheter, intra- and postoperatively, in 21 patients with DCM undergoing decompression surgery. Mean CSFP and cardiac-driven CSFP peak-to-valley amplitude (CSFPp) were analyzed throughout the perioperative period, including the immediate extubation period in eight patients. Intraoperative mean CSFP had a median value and {interquartile range} of 10.8 {5.5} mmHg and increased 1.6-fold to 16.9 {7.1} mmHg postoperatively (p < 0.001). CSFPp increased 3-fold from 0.6 {0.7} to 1.8 {2.5} mmHg (p = 0.001). Increased CSFP persisted overnight. During extubation, there was a notable increase in CSFP and CSFPp of 14.0 {5.8} and 5.1 {3.1} mmHg, respectively. From case-based analysis, this was attributed to an arterial pCO 2 increase. There was no correlation between respirator settings and CSFP metrics. There were distinct and quantifiable changes in CSFP dynamics from the intra- to postoperative setting related to type of respiration, anesthesia, and level of consciousness. When monitoring CSFP dynamics in spine surgery across these settings, cardiorespiratory factors must be controlled for., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Endoscopic spine surgery is an emerging technique of minimally invasive spine surgery. However, headache, seizure, and autonomic dysreflexia are possible irrigation-related complications following full-endoscopic lumbar discectomy (FELD). Pressure elevation through fluid irrigation may contribute to these adverse events. A validated experimental model to investigate parameters for guideline definition is lacking. This study aimed to create an experimental setting for FELD with pressure assessments to prove the concept of repeatable and sensitive measurement of intracranial, intra- and epidural pressures during spine endoscopy., Methods: To measure intradural pressure, catheters were introduced through a sacral approach and advanced to lumbar, thoracic, and cervical levels in human cadavers. Similarly, lumbar epidural and intracranial probes were placed. The dural sac was filled with Ringer solution to a physiologic pressure of 15 cmH2O. Lumbar endoscopy was performed on 3 human cadavers at the L3-4 level. Pressure changes were measured continuously at all sites and the effects of backflow-occlusion were monitored., Results: Reproducibility of the experimental model was validated with catheters at the correct locations and stable compartmental pressure baselines at all levels for 3 specimens (mean±standard deviation: 1.3±2.9 mmHg, 9.0±2.0 mmHg, 6.0±1.2 mmHg, respectively). Pressure increase could be detected sensitively by closing the system with backflow-occlusion., Conclusion: An experimental setup for feasible, repeatable, and precise pressure measurement during FELD in a human cadaveric setup has been developed. This allows investigation of the effects of endoscopic techniques and pump pressures on intra-, epidural and intracranial pressure and enables ranges of safe pump pressures per clinical situations.

Study Design: This study is a scoping review., Objective: There is a broad variability in the definition of degenerative cervical myelopathy (DCM) and no standardized set of diagnostic criteria to date., Methods: We interrogated the Myelopathy.org database, a hand-indexed database of primary clinical studies conducted exclusively on DCM in humans between 2005-2021. The DCM inclusion criteria used in these studies were inputted into 3 topic modeling algorithms: Hierarchical Dirichlet Process (HDP), Latent Dirichlet Allocation (LDA), and BERtopic. The emerging topics were subjected to manual labeling and interpretation., Results: Of 1676 reports, 120 papers (7.16%) had well-defined inclusion criteria and were subjected to topic modeling. Four topics emerged from the HDP model: disturbance from extremity weakness and motor signs; fine-motor and sensory disturbance of upper extremity; a combination of imaging and clinical findings is required for the diagnosis; and "reinforcing" (or modifying) factors that can aid in the diagnosis in borderline cases. The LDA model showed the following topics: disturbance to the patient is required for the diagnosis; reinforcing factors can aid in the diagnosis in borderline cases; clinical findings from the extremities; and a combination of imaging and clinical findings is required for the diagnosis. BERTopic identified the following topics: imaging abnormality, typical clinical features, range of objective criteria, and presence of clinical findings., Conclusions: This review provides quantifiable data that only a minority of past studies in DCM provided meaningful inclusion criteria. The items and patterns found here are very useful for the development of diagnostic criteria for DCM., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Degenerative cervical myelopathy (DCM) is a progressive chronic spinal cord injury estimated to affect 1 in 50 adults. Without standardised guidance, clinical research studies have selected outcomes at their discretion, often underrepresenting the disease and limiting comparability between studies. Utilising a standard minimum data set formed via multi-stakeholder consensus can address these issues. This combines processes to define a core outcome set (COS)-a list of key outcomes-and core data elements (CDEs), a list of key sampling characteristics required to interpret the outcomes. Further "how" these outcomes should be measured and/or reported is then defined in a core measurement set (CMS). This can include a recommendation of a standardised time point at which outcome data should be reported. This study defines a COS, CDE, and CMS for DCM research., Methods and Findings: A minimum data set was developed using a series of modified Delphi processes. Phase 1 involved the setup of an international DCM stakeholder group. Phase 2 involved the development of a longlist of outcomes, data elements, and formation into domains. Phase 3 prioritised the outcomes and CDEs using a two-stage Delphi process. Phase 4 determined the final DCM minimal data set using a consensus meeting. Using the COS, Phase 5 finalised definitions of the measurement construct for each outcome. In Phase 6, a systematic review of the literature was performed, to scope and define the psychometric properties of measurement tools. Phase 7 used a modified Delphi process to inform the short-listing of candidate measurement tools. The final measurement set was then formed through a consensus meeting (Phase 8). To support implementation, the data set was then integrated into template clinical research forms (CRFs) for use in future clinical trials (Phase 9). In total, 28 outcomes and 6 domains (Pain, Neurological Function, Life Impact, Radiology, Economic Impact, and Adverse Events) were entered into the final COS. Thirty two outcomes and 4 domains (Individual, Disease, Investigation, and Intervention) were entered into the final CDE. Finally, 4 outcome instruments (mJOA, NDI, SF-36v2, and SAVES2) were identified for the CMS, with a recommendation for trials evaluating outcomes after surgery, to include baseline measurement and at 6 months from surgery., Conclusions: The AO Spine RECODE-DCM has produced a minimum data set for use in DCM clinical trials today. These are available at https://myelopathy.org/minimum-dataset/. While it is anticipated the CDE and COS have strong and durable relevance, it is acknowledged that new measurement tools, alongside an increasing transition to study patients not undergoing surgery, may necessitate updates and adaptation, particularly with respect to the CMS., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Davies et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: New diagnostic techniques are a substantial research focus in degenerative cervical myelopathy (DCM). This cross-sectional study determined the significance of cardiac-related spinal cord motion and the extent of spinal stenosis as indicators of mechanical strain on the cord., Methods: Eighty-four DCM patients underwent MRI/clinical assessments and were classified as MRI+ [T2-weighted (T2w) hyperintense lesion in MRI] or MRI- (no T2w-hyperintense lesion). Cord motion (displacement assessed by phase-contrast MRI) and spinal stenosis [adapted spinal canal occupation ratio (aSCOR)] were related to neurological (sensory/motor) and neurophysiological readouts [contact heat evoked potentials (CHEPs)] by receiver operating characteristic (ROC) analysis., Results: MRI+ patients ( N  = 31; 36.9%) were more impaired compared to MRI- patients ( N  = 53; 63.1%) based on the modified Japanese Orthopedic Association (mJOA) subscores for upper {MRI+ [median (Interquartile range)]: 4 (4-5); MRI-: 5 (5-5); p  < 0.01} and lower extremity [MRI+: 6 (6-7); MRI-: 7 (6-7); p  = 0.03] motor dysfunction and the monofilament score [MRI+: 21 (18-23); MRI-: 24 (22 - 24); p  < 0.01]. Both patient groups showed similar extent of cord motion and stenosis. Only in the MRI- group displacement identified patients with pathologic assessments [trunk/lower extremity pin prick score (T/LEPP): AUC = 0.67, p  = 0.03; CHEPs: AUC = 0.73, p  = 0.01]. Cord motion thresholds: T/LEPP: 1.67 mm (sensitivity 84.6%, specificity 52.5%); CHEPs: 1.96 mm (sensitivity 83.3%, specificity 65.6%). The aSCOR failed to show any relation to the clinical assessments., Discussion: These findings affirm cord motion measurements as a promising additional biomarker to improve the clinical workup and to enable timely surgical treatment particularly in MRI- DCM patients., Clinical Trial Registration: www.clinicaltrials.gov, NCT02170155., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pfender, Jutzeler, Hubli, Scheuren, Pfyffer, Zipser, Rosner, Friedl, Sutter, Spirig, Betz, Schubert, Seif, Freund, Farshad, Curt and Hupp.)

Study Design: Topic modeling of literature., Objectives: Our study has 2 goals: (i) to clarify key themes in degenerative cervical myelopathy (DCM) research, and (ii) to evaluate the current trends in the popularity or decline of these topics. Additionally, we aim to highlight the potential of natural language processing (NLP) in facilitating research syntheses., Methods: Documents were retrieved from Scopus, preprocessed, and modeled using BERTopic, an NLP-based topic modeling method. We specified a minimum topic size of 25 documents and 50 words per topic. After the models were trained, they generated a list of topics and corresponding representative documents. We utilized linear regression models to examine trends within the identified topics. In this context, topics exhibiting increasing linear slopes were categorized as "hot topics," while those with decreasing slopes were categorized as "cold topics"., Results: Our analysis retrieved 3510 documents that were classified into 21 different topics. The 3 most frequently occurring topics were "OPLL" (ossification of the posterior longitudinal ligament), "Anterior Fusion," and "Surgical Outcomes." Trend analysis revealed the hottest topics of the decade to be "Animal Models," "DCM in the Elderly," and "Posterior Decompression" while "Morphometric Analyses," "Questionnaires," and "MEP and SSEP" were identified as being the coldest topics., Conclusions: Our NLP methodology conducted a thorough and detailed analysis of DCM research, uncovering valuable insights into research trends that were otherwise difficult to discern using traditional techniques. The results provide valuable guidance for future research directions, policy considerations, and identification of emerging trends., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Study Design: Development of a clinical practice guideline following the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) process., Objective: The objectives of this study were to develop guidelines that outline the utility of intraoperative neuromonitoring (IONM) to detect intraoperative spinal cord injury (ISCI) among patients undergoing spine surgery, to define a subset of patients undergoing spine surgery at higher risk for ISCI and to develop protocols to prevent, diagnose, and manage ISCI., Methods: All systematic reviews were performed according to PRISMA standards and registered on PROSPERO. A multidisciplinary, international Guidelines Development Group (GDG) reviewed and discussed the evidence using GRADE protocols. Consensus was defined by 80% agreement among GDG members. A systematic review and diagnostic test accuracy (DTA) meta-analysis was performed to synthesize pooled evidence on the diagnostic accuracy of IONM to detect ISCI among patients undergoing spinal surgery. The IONM modalities evaluated included somatosensory evoked potentials (SSEPs), motor evoked potentials (MEPs), electromyography (EMG), and multimodal neuromonitoring. Utilizing this knowledge and their clinical experience, the multidisciplinary GDG created recommendations for the use of IONM to identify ISCI in patients undergoing spine surgery. The evidence related to existing care pathways to manage ISCI was summarized and based on this a novel AO Spine-PRAXIS care pathway was created., Results: Our recommendations are as follows: (1) We recommend that intraoperative neurophysiological monitoring be employed for high risk patients undergoing spine surgery, and (2) We suggest that patients at "high risk" for ISCI during spine surgery be proactively identified, that after identification of such patients, multi-disciplinary team discussions be undertaken to manage patients, and that an intraoperative protocol including the use of IONM be implemented. A care pathway for the prevention, diagnosis, and management of ISCI has been developed by the GDG., Conclusion: We anticipate that these guidelines will promote the use of IONM to detect and manage ISCI, and promote the use of preoperative and intraoperative checklists by surgeons and other team members for high risk patients undergoing spine surgery. We welcome teams to implement and evaluate the care pathway created by our GDG., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Study Design: Clinical practice guideline development., Objectives: Acute spinal cord injury (SCI) can result in devastating motor, sensory, and autonomic impairment; loss of independence; and reduced quality of life. Preclinical evidence suggests that early decompression of the spinal cord may help to limit secondary injury, reduce damage to the neural tissue, and improve functional outcomes. Emerging evidence indicates that "early" surgical decompression completed within 24 hours of injury also improves neurological recovery in patients with acute SCI. The objective of this clinical practice guideline (CPG) is to update the 2017 recommendations on the timing of surgical decompression and to evaluate the evidence with respect to ultra-early surgery (in particular, but not limited to, <12 hours after acute SCI)., Methods: A multidisciplinary, international, guideline development group (GDG) was formed that consisted of spine surgeons, neurologists, critical care specialists, emergency medicine doctors, physical medicine and rehabilitation professionals, as well as individuals living with SCI. A systematic review was conducted based on accepted methodological standards to evaluate the impact of early (within 24 hours of acute SCI) or ultra-early (in particular, but not limited to, within 12 hours of acute SCI) surgery on neurological recovery, functional outcomes, administrative outcomes, safety, and cost-effectiveness. The GRADE approach was used to rate the overall strength of evidence across studies for each primary outcome. Using the "evidence-to-recommendation" framework, recommendations were then developed that considered the balance of benefits and harms, financial impact, patient values, acceptability, and feasibility. The guideline was internally appraised using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool., Results: The GDG recommended that early surgery (≤24 hours after injury) be offered as the preferred option for adult patients with acute SCI regardless of level. This recommendation was based on moderate evidence suggesting that patients were 2 times more likely to recover by ≥ 2 ASIA Impairment Score (AIS) grades at 6 months (RR: 2.76, 95% CI 1.60 to 4.98) and 12 months (RR: 1.95, 95% CI 1.26 to 3.18) if they were decompressed within 24 hours compared to after 24 hours. Furthermore, patients undergoing early surgery improved by an additional 4.50 (95% 1.70 to 7.29) points on the ASIA Motor Score compared to patients undergoing surgery after 24 hours post-injury. The GDG also agreed that a recommendation for ultra-early surgery could not be made on the basis of the current evidence because of the small sample sizes, variable definitions of what constituted ultra-early in the literature, and the inconsistency of the evidence., Conclusions: It is recommended that patients with an acute SCI, regardless of level, undergo surgery within 24 hours after injury when medically feasible. Future research is required to determine the differential effectiveness of early surgery in different subpopulations and the impact of ultra-early surgery on neurological recovery. Moreover, further work is required to define what constitutes effective spinal cord decompression and to individualize care. It is also recognized that a concerted international effort will be required to translate these recommendations into policy., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest concerning the research, authorship, and/or publication of this article.

Study Design: Clinical practice guideline development following the GRADE process., Objectives: Hemodynamic management is one of the only available treatment options that likely improves neurologic outcomes in patients with acute traumatic spinal cord injury (SCI). Augmenting mean arterial pressure (MAP) aims to improve blood perfusion and oxygen delivery to the injured spinal cord in order to minimize secondary ischemic damage to neural tissue. The objective of this guideline was to update the 2013 AANS/CNS recommendations on the hemodynamic management of patients with acute traumatic SCI, acknowledging that much has been published in this area since its publication. Specifically, we sought to make recommendations on 1. The range of mean arterial pressure (MAP) to be maintained by identifying an upper and lower MAP limit; 2. The duration of such MAP augmentation; and 3. The choice of vasopressor. Additionally, we sought to make a recommendation on spinal cord perfusion pressure (SCPP) targets., Methods: A multidisciplinary guideline development group (GDG) was formed that included health care professionals from a wide range of clinical specialities, patient advocates, and individuals living with SCI. The GDG reviewed the 2013 AANS/CNS guidelines and voted on whether each recommendation should be endorsed or updated. A systematic review of the literature, following PRISMA standards and registered in PROSPERO, was conducted to inform the guideline development process and address the following key questions: (i) what are the effects of goal-directed interventions to optimize spinal cord perfusion on extent of neurological recovery and rates of adverse events at any time point of follow-up? and (ii) what are the effects of particular monitoring techniques, perfusion ranges, pharmacological agents, and durations of treatment on extent of neurological recovery and rates of adverse events at any time point of follow-up? The GDG combined the information from this systematic review with their clinical expertise in order to develop recommendations on a MAP target range (specifically an upper and lower limit to target), the optimal duration for MAP augmentation, and the use of vasopressors or inotropes. Using methods outlined by the GRADE working group, recommendations were formulated that considered the balance of benefits and harms, financial impact, acceptability, feasibility and patient preferences., Results: The GDG suggested that MAP should be augmented to at least 75-80 mmHg as the "lower limit," but not actively augmented beyond an "upper limit" of 90-95 mmHg in order to optimize spinal cord perfusion in acute traumatic SCI. The quality of the evidence around the "target MAP" was very low, and thus the strength of this recommendation is weak. For duration of hemodynamic management, the GDG "suggested" that MAP be augmented for a duration of 3-7 days. Again, the quality of the evidence around the duration of MAP support was very low, and thus the strength of this recommendation is also weak. The GDG felt that a recommendation on the choice of vasopressor or the use of SCPP targets was not warranted, given the dearth of available evidence., Conclusion: We provide new recommendations for blood pressure management after acute SCI that acknowledge the limitations of the current evidence on the relationship between MAP and neurologic recovery. It was felt that the low quality of existing evidence and uncertainty around the relationship between MAP and neurologic recovery justified a greater range of MAP to target, and for a broader range of days post-injury than recommended in previous guidelines. While important knowledge gaps still remain regarding hemodynamic management, these recommendations represent current perspectives on the role of MAP augmentation for acute SCI., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Study Design: Modified DELPHI Consensus Process., Objective: To agree a single unifying term and definition. Globally, cervical myelopathy caused by degenerative changes to the spine is known by over 11 different names. This inconsistency contributes to many clinical and research challenges, including a lack of awareness., Method: AO Spine RECODE-DCM (Research objectives and Common Data Elements Degenerative Cervical Myelopathy). To determine the index term, a longlist of candidate terms and their rationale, was created using a literature review and interviews. This was shared with the community, to select their preferred terms (248 members (58%) including 149 (60%) surgeons, 45 (18%) other healthcare professionals and 54 (22%) People with DCM or their supporters) and finalized using a consensus meeting. To determine a definition, a medical definition framework was created using inductive thematic analysis of selected International Classification of Disease definitions. Separately, stakeholders submitted their suggested definition which also underwent inductive thematic analysis (317 members (76%), 190 (59%) surgeons, 62 (20%) other healthcare professionals and 72 (23%) persons living with DCM or their supporters). Using this definition framework, a working definition was created based on submitted content, and finalized using consensus meetings., Results: Degenerative Cervical Myelopathy was selected as the unifying term, defined in short, as a progressive spinal cord injury caused by narrowing of the cervical spinal canal., Conclusion: A consistent term and definition can support education and research initiatives. This was selected using a structured and iterative methodology, which may serve as an exemplar for others in the future., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Traumatic spinal cord injury (SCI) may occur across the lifespan and is of global relevance. Damage of the spinal cord results in para- or tetraplegia and is associated with neuropathic pain, spasticity, respiratory, and autonomic dysfunction (i.e., control of bladder-bowel function). While the acute surgical treatment aims at stabilizing the spine and decompressing the damaged spinal cord, SCI patients require neurorehabilitation to restore neural function and to compensate for any impairments including motor disability, pain treatment, and bladder/bowel management. However, the spinal cord has a limited capacity to regenerate and much of the disability may persist, depending on the initial lesion severity and level of injury. For this reason, and the lack of effective drug treatments, there is an emerging interest and urgent need in promoting axonal regeneration and remyelination after SCI through cell- and stem-cell based therapies. This review briefly summarizes the state-of the art management of acute SCI and its neurorehabilitation to critically appraise phase I/II trials from the last two decades that have investigated cell-based therapies (i.e., Schwann cells, macrophages, and olfactory ensheathing cells) and stem cell-based therapies (i.e., neural stem cells, mesenchymal, and hematopoietic stem cells). Recently, two large multicenter trials provided evidence for the safety and feasibility of neural stem cell transplantation into the injured cord, whilst two monocenter trials also showed this to be the case for the transplantation of Schwann cells into the posttraumatic cord cavity. These are milestone studies that will facilitate further interventional trials. However, the clinical adoption of such approaches remains unproven, as there is only limited encouraging data, often in single patients, and no proven trial evidence to support regulatory approval., (Copyright © 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Although many frailty tools have been used to predict traumatic spinal injury (TSI) outcomes, identifying predictors of outcomes after TSI in the aged population is difficult. Frailty, age, and TSI association are interesting topics of discussion in geriatric literature. However, the association between these variables are yet to be clearly elucidated. We conducted a systematic review to investigate the association between frailty and TSI outcomes. The authors searched Medline, EMBASE, Scopus, and Web of Science for relevant studies. Studies with observational designs that assessed baseline frailty status in individuals suffering from TSI published from inception until 26th March 2023 were included. Length of hospital stay (LoS), adverse events (AEs), and mortality were the outcomes of interest. Of the 2425 citations, 16 studies involving 37,640 participants were included. The modified frailty index (mFI) was the most common tool used to assess frailty. Meta-analysis was employed only in studies that used mFI for measuring frailty. Frailty was significantly associated with increased in-hospital or 30-day mortality (pooled odds ratio [OR]: 1.93 [1.19; 3.11]), non-routine discharge (pooled OR: 2.44 [1.34; 4.44]), and AEs or complications (pooled OR: 2.00 [1.14; 3.50]). However, no significant relationship was found between frailty and LoS (pooled OR: 3.02 [0.86; 10.60]). Heterogeneity was observed across multiple factors, including age, injury level, frailty assessment tool, and spinal cord injury characteristics. In conclusion, although there is limited data concerning using frailty scales to predict short-term outcomes after TSI, the results showed that frailty status may be a predictor of in-hospital mortality, AEs, and unfavorable discharge destination.

Introduction: Degenerative cervical myelopathy (DCM) is the most common cause of non-traumatic incomplete spinal cord injury, but its pathophysiology is poorly understood. As spinal cord compression observed in standard MRI often fails to explain a patient's status, new diagnostic techniques to assess DCM are one of the research priorities. Minor cardiac-related cranio-caudal oscillations of the cervical spinal cord are observed by phase-contrast MRI (PC-MRI) in healthy controls (HCs), while they become pathologically increased in patients suffering from degenerative cervical myelopathy. Whether transversal oscillations (i.e., anterior-posterior and right-left) also change in DCM patients is not known., Methods: We assessed spinal cord motion simultaneously in all three spatial directions (i.e., cranio-caudal, anterior-posterior, and right-left) using sagittal PC-MRI and compared physiological oscillations in 18 HCs to pathological changes in 72 DCM patients with spinal canal stenosis. The parameter of interest was the amplitude of the velocity signal (i.e., maximum positive to maximum negative peak) during the cardiac cycle., Results: Most patients suffered from mild DCM (mJOA score 16 (14-18) points), and the majority (68.1%) presented with multisegmental stenosis. The spinal canal was considerably constricted in DCM patients in all segments compared to HCs. Under physiological conditions in HCs, the cervical spinal cord oscillates in the cranio-caudal and anterior-posterior directions, while right-left motion was marginal [e.g., segment C5 amplitudes: cranio-caudal: 0.40 (0.27-0.48) cm/s; anterior-posterior: 0.18 (0.16-0.29) cm/s; right-left: 0.10 (0.08-0.13) cm/s]. Compared to HCs, DCM patients presented with considerably increased cranio-caudal oscillations due to the cardinal pathophysiologic change in non-stenotic [e.g., segment C5 amplitudes: 0.79 (0.49-1.32) cm/s] and stenotic segments [.g., segment C5 amplitudes: 0.99 (0.69-1.42) cm/s]). In contrast, right-left [e.g., segment C5 amplitudes: non-stenotic segment: 0.20 (0.13-0.32) cm/s; stenotic segment: 0.11 (0.09-0.18) cm/s] and anterior-posterior oscillations [e.g., segment C5 amplitudes: non-stenotic segment: 0.26 (0.15-0.45) cm/s; stenotic segment: 0.11 (0.09-0.18) cm/s] remained on low magnitudes comparable to HCs., Conclusion: Increased cranio-caudal oscillations of the cervical cord are the cardinal pathophysiologic change and can be quantified using PC-MRI in DCM patients. This study addresses spinal cord oscillations as a relevant biomarker reflecting dynamic mechanical cord stress in DCM patients, potentially contributing to a loss of function., Competing Interests: MK was employed by the Siemens Healthineers AG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pfender, Rosner, Zipser, Friedl, Schubert, Sutter, Klarhoefer, Spirig, Betz, Freund, Farshad, Curt and Hupp.)

Delirium incidence and phenotype differ between sexes. Sex differences in the selection of treatment strategies remain elusive. We evaluated sex-specific responses to non- and pharmacological management. In this observational prospective cohort study conducted at the University Hospital Zurich, Switzerland, 602 patients managed for delirium were analyzed. Remission and benefit ratios of treatments were calculated using Cox regression models. Baseline characteristics were similar in both sexes. Overall, 89% of all patients (540/602) received pharmacological management for delirium, most (77%) with one or two different medications. An equal number of male and female patients had either no medication ( P  = 0.321) or three and more medications ( P  = 0.797). Men had two different medications more often ( P  = 0.009), while women more frequently received one medication ( P  = 0.037). Remission rates within 20 days were higher in non-pharmacological treatment and similar between sexes, with odds of 1.36 in females, and 2.3 in males. Non-pharmacological treatment was equally efficacious in both sexes. Women who received supportive treatment and monotherapy had equal odds of remission. Men fared better with supportive care compared to pharmacologic therapies. Remission rates with different management strategies were similar between sexes. No sex differences were found regarding phenotypes, clinical course, and response to therapy., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Health care decisions are a critical determinant in the evolution of chronic illness. In shared decision-making (SDM), patients and clinicians work collaboratively to reach evidence-based health decisions that align with individual circumstances, values, and preferences. This personalized approach to clinical care likely has substantial benefits in the oversight of degenerative cervical myelopathy (DCM), a type of nontraumatic spinal cord injury. Its chronicity, heterogeneous clinical presentation, complex management, and variable disease course engenders an imperative for a patient-centric approach that accounts for each patient's unique needs and priorities. Inadequate patient knowledge about the condition and an incomplete understanding of the critical decision points that arise during the course of care currently hinder the fruitful participation of health care providers and patients in SDM. This study protocol presents the rationale for deploying SDM for DCM and delineates the groundwork required to achieve this., Objective: The study's primary outcome is the development of a comprehensive checklist to be implemented upon diagnosis that provides patients with essential information necessary to support their informed decision-making. This is known as a core information set (CIS). The secondary outcome is the creation of a detailed process map that provides a diagrammatic representation of the global care workflows and cognitive processes involved in DCM care. Characterizing the critical decision points along a patient's journey will allow for an effective exploration of SDM tools for routine clinical practice to enhance patient-centered care and improve clinical outcomes., Methods: Both CISs and process maps are coproduced iteratively through a collaborative process involving the input and consensus of key stakeholders. This will be facilitated by Myelopathy.org, a global DCM charity, through its Research Objectives and Common Data Elements for Degenerative Cervical Myelopathy community. To develop the CIS, a 3-round, web-based Delphi process will be used, starting with a baseline list of information items derived from a recent scoping review of educational materials in DCM, patient interviews, and a qualitative survey of professionals. A priori criteria for achieving consensus are specified. The process map will be developed iteratively using semistructured interviews with patients and professionals and validated by key stakeholders., Results: Recruitment for the Delphi consensus study began in April 2023. The pilot-testing of process map interview participants started simultaneously, with the formulation of an initial baseline map underway., Conclusions: This protocol marks the first attempt to provide a starting point for investigating SDM in DCM. The primary work centers on developing an educational tool for use in diagnosis to enable enhanced onward decision-making. The wider objective is to aid stakeholders in developing SDM tools by identifying critical decision junctures in DCM care. Through these approaches, we aim to provide an exhaustive launchpad for formulating SDM tools in the wider DCM community., International Registered Report Identifier (irrid): DERR1-10.2196/46809., (©Irina Sangeorzan, Grazia Antonacci, Anne Martin, Ben Grodzinski, Carl M Zipser, Rory K J Murphy, Panoraia Andriopoulou, Chad E Cook, David B Anderson, James Guest, Julio C Furlan, Mark R N Kotter, Timothy F Boerger, Iwan Sadler, Elizabeth A Roberts, Helen Wood, Christine Fraser, Michael G Fehlings, Vishal Kumar, Josephine Jung, James Milligan, Aria Nouri, Allan R Martin, Tammy Blizzard, Luiz Roberto Vialle, Lindsay Tetreault, Sukhvinder Kalsi-Ryan, Anna MacDowall, Esther Martin-Moore, Martin Burwood, Lianne Wood, Abdul Lalkhen, Manabu Ito, Nicky Wilson, Caroline Treanor, Sheila Dugan, Benjamin M Davies. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 09.10.2023.)

Introduction: A delirium can be encountered in almost all hospital sectors. The prevalence varies between 20 and 40 % in internal medicine and surgical wards and between 50 and 60 % in palliative care and intensive care units. A delirium is characterized by impaired attention, consciousness, and cognitive impairment with acute onset and fluctuating course. People with delirium have inferior clinical outcomes, including higher mortality and more need for long-term care after discharge. This article first reviews the clinical and pathophysiologic basis of delirium, followed by a detailed description of individual risk profiles based on a prospective, hospital-wide cohort study (Delir-Path) conducted at the University Hospital Zurich. We will then give a brief update on diagnosis and management of delirium and an outlook on how neurophysiology and blood biomarkers can complement delirium care in the future., Competing Interests: Es bestehen keine Interessenskonflikte, (© 2023 Aerzteverlag medinfo AG.)

Objectives: To explore whether a James Lind Alliance Priority Setting Partnership could provide insights on knowledge translation within the field of degenerative cervical myelopathy (DCM)., Design: Secondary analysis of a James Lind Alliance Priority Setting Partnership process for DCM., Participants and Setting: DCM stake holders, including spinal surgeons, people with myelopathy and other healthcare professionals, were surveyed internationally. Research suggestions submitted by stakeholders but considered answered were identified. Sampling characteristics of respondents were compared with the overall cohort to identify subgroups underserved by current knowledge translation., Results: The survey was completed by 423 individuals from 68 different countries. A total of 22% of participants submitted research suggestions that were considered 'answered'. There was a significant difference between responses from different stakeholder groups (p<0.005). Spinal surgeons were the group which was most likely to submit an 'answered' research question. Respondents from South America were also most likely to submit 'answered' questions, when compared with other regions. However, there was no significant difference between responses from different stakeholder regions (p=0.4)., Conclusions: Knowledge translation challenges exist within DCM. This practical approach to measuring knowledge translation may offer a more responsive assessment to guide interventions, complementing existing metrics., Competing Interests: Competing interests: BD, JB, ODM, IS, ES, MGF and MRNK have voluntary roles at Myelopathy.org, an international DCM charity., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Intramuscular high-frequency coherence is increased during visually guided treadmill walking as a consequence of increased supra-spinal input. The influence of walking speed on intramuscular coherence and its inter-trial reproducibility need to be established before adoption as a functional gait assessment tool in clinical settings. Here, fifteen healthy controls performed a normal and a target walking task on a treadmill at various speeds (0.3 m/s, 0.5 m/s, 0.9 m/s, and preferred) during two sessions. Intramuscular coherence was calculated between two surface EMG recordings sites of the Tibialis anterior muscle during the swing phase of walking. The results were averaged across low-frequency (5-14 Hz) and high-frequency (15-55 Hz) bands. The effect of speed, task, and time on mean coherence was assessed using three-way repeated measures ANOVA. Reliability and agreement were calculated with the intra-class correlation coefficient and Bland-Altman method, respectively. Intramuscular coherence during target walking was significantly higher than during normal walking across all walking speeds in the high-frequency band as obtained by the three-way repeated measures ANOVA. Interaction effects between task and speed were found for the low- and high-frequency bands, suggesting that task-dependent differences increase at higher walking speeds. Reliability of intramuscular coherence was moderate to excellent for most normal and target walking tasks in all frequency bands. This study confirms previous reports of increased intramuscular coherence during target walking, while providing first evidence for reproducibility and robustness of this measure as a requirement to investigate supra-spinal input.Trial registration Registry number/ClinicalTrials.gov Identifier: NCT03343132, date of registration 2017/11/17., (© 2023. The Author(s).)

Purpose: Before the era of spinal imaging, presence of a spinal canal block was tested through gross changes in cerebrospinal fluid pressure (CSFP) provoked by manual compression of the jugular veins (referred to as Queckenstedt's test; QT). Beyond these provoked gross changes, cardiac-driven CSFP peak-to-valley amplitudes (CSFPp) can be recorded during CSFP registration. This is the first study to assess whether the QT can be repurposed to derive descriptors of the CSF pulsatility curve, focusing on feasibility and repeatability., Method: Lumbar puncture was performed in lateral recumbent position in fourteen elderly patients (59.7±9.3 years, 6F) (NCT02170155) without stenosis of the spinal canal. CSFP was recorded during resting state and QT. A surrogate for the relative pulse pressure coefficient was computed from repeated QTs (i.e., RPPC-Q)., Results: Resting state mean CSFP was 12.3 mmHg (IQR 3.2) and CSFPp was 1.0 mmHg (0.5). Mean CSFP rise during QT was 12.5 mmHg (7.3). CSFPp showed an average 3-fold increase at peak QT compared to the resting state. Median RPPC-Q was 0.18 (0.04). There was no systematic error in the computed metrics between the first and second QT., Conclusion: This technical note describes a method to reliably derive, beyond gross CSFP increments, metrics related to cardiac-driven amplitudes during QT (i.e., RPPC-Q). A study comparing these metrics as obtained by established procedures (i.e., infusion testing) and by QT is warranted., (© 2023. The Author(s).)

Background: Sufficient and timely spinal cord decompression is a critical surgical objective for neurological recovery in spinal cord injury (SCI). Residual cord compression may be associated with disturbed cerebrospinal fluid pressure (CSFP) dynamics., Objectives: This study aims to assess whether intrathecal CSFP dynamics in SCI following surgical decompression are feasible and safe, and to explore the diagnostic utility., Methods: Prospective cohort study. Bedside lumbar CSFP dynamics and cervical MRI were obtained following surgical decompression in N = 9 with mostly cervical acute-subacute SCI and N = 2 patients with non-traumatic SCI. CSFP measurements included mean CSFP, cardiac-driven CSFP peak-to-valley amplitudes (CSFPp), Valsalva maneuver, and Queckenstedt's test (firm pressure on jugular veins, QT). From QT, proxies for cerebrospinal fluid pulsatility curve were calculated (ie, relative pulse pressure coefficient; RPPC-Q). CSFP metrics were compared to spine-healthy patients. computer tomography (CT)-myelography was done in 3/8 simultaneous to CSFP measurements., Results: Mean age was 45 ± 9 years (range 17-67; 3F), SCI was complete (AIS A, N = 5) or incomplete (AIS B-D, N = 6). No adverse events related to CSFP assessments. CSFP rise during QT was induced in all patients [range 9.6-26.6 mmHg]. However, CSFPp was reduced in 3/11 (0.1-0.3 mmHg), and in 3/11 RPPC-Q was abnormal (0.01-0.05). Valsalva response was reduced in 8/11 (2.6-23.4 mmHg). CSFP dynamics corresponded to CT-myelography., Conclusions: Comprehensive bedside lumbar CSFP dynamics in SCI following decompression are safe, feasible, and can reveal distinct patterns of residual spinal cord compression. Longitudinal studies are required to define critical thresholds of impaired CSFP dynamics that may impact neurological recovery and requiring surgical revisions.

Background and Aims: Delirium is the most common acute neuropsychiatric syndrome in hospitalized patients. Higher age and cognitive impairment are known predisposing risk factors in general hospital populations. However, the interrelation with precipitating gastrointestinal (GI) and hepato-pancreato-biliary (HPB) diseases remains to be determined., Patients and Methods: Prospective 1-year hospital-wide cohort study in 29'278 adults, subgroup analysis in 718 patients hospitalized with GI/HPB disease. Delirium based on routine admission screening and a DSM-5 based construct. Regression analyses used to evaluate clinical characteristics of delirious patients., Results: Delirium was detected in 24.8% (178/718). Age in delirious patients (median 62 years [IQR 21]) was not different to non-delirious (median 60 years [IQR 22]), p = 0.45). Dementia was the strongest predisposing factor for delirium (OR 66.16 [6.31-693.83], p < 0.001). Functional impairment, and at most, immobility increased odds for delirium (OR 7.78 [3.84-15.77], p < 0.001). Patients with delirium had higher in-hospital mortality rates (18%; OR 39.23 [11.85-129.93], p < 0.001). From GI and HPB conditions, cirrhosis predisposed to delirium (OR 2.11 [1.11-4.03], p = 0.023), while acute renal failure (OR 4.45 [1.61-12.26], p = 0.004) and liver disease (OR 2.22 [1.12-4.42], p = 0.023) were precipitators. Total costs were higher in patients with delirium (USD 30003 vs. 10977; p < 0.001)., Conclusion: Delirium in GI- and HPB-disease was not associated with higher age per se , but with cognitive and functional impairment. Delirium needs to be considered in younger adults with acute renal failure and/or liver disease. Clinicians should be aware about individual risk profiles, apply preventive and supportive strategies early, which may improve outcomes and lower costs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hildenbrand, Murray, von Känel, Deibel, Schreiner, Ernst, Zipser and Böettger.)

Background and Purpose: The timing of decision-making for a surgical intervention in patients with mild degenerative cervical myelopathy (DCM) is challenging. Spinal cord motion phase contrast MRI (PC-MRI) measurements can reveal the extent of dynamic mechanical strain on the spinal cord to potentially identify high-risk patients. This study aims to determine the comparability of axial and sagittal PC-MRI measurements of spinal cord motion with the prospect of improving the clinical workup., Methods: Sixty-four DCM patients underwent a PC-MRI scan assessing spinal cord motion. The agreement of axial and sagittal measurements was determined by means of intraclass correlation coefficients (ICCs) and Bland-Altman analyses., Results: The comparability of axial and sagittal PC-MRI measurements was good to excellent at all cervical levels (ICCs motion amplitude: .810-.940; p &lt; .001). Significant differences between axial and sagittal amplitude values could be found at segments C3 and C4, while its magnitude was low (C3: 0.07 ± 0.19 cm/second; C4: -0.12 ± 0.30 cm/second). Bland-Altman analysis showed a good agreement between axial and sagittal PC-MRI scans (coefficients of repeatability: minimum -0.23 cm/second at C2; maximum -0.58 cm/second at C4). Subgroup analysis regarding anatomic conditions (stenotic vs. nonstenotic segments) and different velocity encoding (2 vs. 3 cm/second) showed comparable results., Conclusions: This study demonstrates good comparability between axial and sagittal spinal cord motion measurements in DCM patients. To this end, axial and sagittal PC-MRI are both accurate and sensitive in detecting pathologic cord motion. Therefore, such measures could identify high-risk patients and improve clinical decision-making (ie, timing of decompression)., (© 2022 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

Competing Interests: The authors report no conflicts of interest.

Spinal canal narrowing with consecutive spinal cord compression is considered a key mechanism in degenerative cervical myelopathy (DCM). DCM is a common spine condition associated with progressive neurological disability, and timely decompressive surgery is recommended. However, the clinical and radiological diagnostic workup is often ambiguous, challenging confident proactive treatment recommendations. Cerebrospinal fluid pressure dynamics (CSFP) are altered by spinal canal narrowing. Therefore, we aim to explore the potential value of bedside CSFP assessments for qualitative and quantitative assessment of spinal canal narrowing in DCM. In this prospective case series, seven patients with DCM underwent bedside lumbar puncture with measurement of CSFP dynamics and routine CSF analysis (NCT02170155). The patients were enrolled when standard diagnostic algorithms did not permit a clear treatment decision. Measurements include baseline CSFP, cardiac-driven CSFP peak-to-trough amplitude (CSFPp), and the Queckenstedt's test (firm pressure on jugular veins) in neutral and reclined head position. From the Queckenstedt's test, proxies for craniospinal elastance (i.e., relative pulse pressure coefficient; RPPC-Q) were calculated analogously to infusion testing. CSFP metrics were deemed suspicious of canal narrowing when numbers were lower than the minimum value from a previously tested elderly spine-healthy cohort ( N = 14). Mean age was 56 ± 13 years (range, 38-75; 2F); symptom severity was mostly mild to moderate (mean mJOA, 13.5 ± 2.6; range, 9-17). All the patients showed some extent of cervical stenosis in the MRI of unclear significance (5/7 following decompressive cervical spine surgery with an adjacent level or residual stenosis). Baseline CSFP was normal except for one patient (range, 4.7-17.4 mmHg). Normal values were found for CSFPp (0.4-1.3 mmHg) and the Queckenstedt's test in normal head positioning (9.-25.3 mmHg). During reclination, the Queckenstedt's test significantly decreased in one, and CSFPp in another case (>50% compared to normal position). RPPC-Q (0.07-0.19) aligned with lower values from spine-healthy (0.10-0.44). Routine CSF examinations showed mild total protein elevation (mean, 522 ± 108 mg/ml) without further evidence for the disturbed blood brain barrier. Intrathecal CSFP measurements allow discerning disturbed from normal CSFP dynamics in this population. Prospective longitudinal studies should further evaluate the diagnostic utility of CSFP assessments in DCM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kheram, Pfender, Boraschi, Farshad, Kurtcuoglu, Curt, Schubert and Zipser.)

Individuals regaining reliable day-to-day walking function after incomplete spinal cord injury (iSCI) report persisting unsteadiness when confronted with walking challenges. However, quantifiable measures of walking capacity lack the sensitivity to reveal underlying impairments of supra-spinal locomotor control. This study investigates the relationship between intramuscular coherence and corticospinal dynamic balance control during a visually guided Target walking treadmill task. In thirteen individuals with iSCI and 24 controls, intramuscular coherence and cumulant densities were estimated from pairs of Tibialis anterior surface EMG recordings during normal treadmill walking and a Target walking task. The approximate center of mass was calculated from pelvis markers. Spearman rank correlations were performed to evaluate the relationship between intramuscular coherence, clinical parameters, and center of mass parameters. In controls, we found that the Target walking task results in increased high-frequency (21-44 Hz) intramuscular coherence, which negatively related to changes in the center of mass movement, whereas this modulation was largely reduced in individuals with iSCI. The impaired modulation of high-frequency intramuscular coherence during the Target walking task correlated with neurophysiological and functional readouts, such as motor-evoked potential amplitude and outdoor mobility score, as well as center of mass trajectory length. The Target walking effect, the difference between Target and Normal walking intramuscular coherence, was significantly higher in controls than in individuals with iSCI [ F (1.0,35.0) = 13.042, p < 0.001]. Intramuscular coherence obtained during challenging walking in individuals with iSCI may provide information on corticospinal gait control. The relationships between biomechanics, clinical scores, and neurophysiology suggest that intramuscular coherence assessed during challenging tasks may be meaningful for understanding impaired supra-spinal control in individuals with iSCI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zipser-Mohammadzada, Conway, Halliday, Zipser, Easthope, Curt and Schubert.)

Objectives: Delirium is known to contribute to increased rates of institutionalization and mortality. The full extent of adverse outcomes, however, remains understudied. We aimed to systematically assess the discharge destinations and mortality risk in delirious patients in a large sample across all hospital services., Design: Pragmatic prospective cohort study of consecutive admissions to a large health care system., Setting and Participants: A total of 27,026 consecutive adults (>18 years old) with length of stay of at least 24 hours in a tertiary care center from January 1 to December 31, 2014., Methods: Presence of delirium determined by routine delirium screening. Clinical characteristics, discharge destination, and mortality were collected. Calculation of odds ratios (ORs) with logistic regression with adjustment for age, sex, and Charlson comorbidity index (CCI)., Results: Delirium was detected in 19.7% of patients (5313 of 27,026), median age of delirious patients was 56 years (25-75 interquartile range = 37-70). The electronic health record (DSM-5-based) delirium algorithm correctly identified 93.3% of delirium diagnoses made by consultation-liaison psychiatrists. Across services, the odds of delirious patients returning home was significantly reduced [OR 0.12; confidence interval (CI) 0.10-0.13; P < .001]. Rather, these patients were transferred to acute rehabilitation (OR 4.15; CI 3.78-4.55; P < .001) or nursing homes (OR 4.12; CI 3.45-4.93; P < .001). Delirious patients had a significantly increased adjusted mortality risk (OR 30.0; CI 23.2-39.4; P < .001)., Conclusions and Implications: This study advances our understanding of the discharge destination across all services in adults admitted to a large hospital system. Delirium was associated with reduced odds of returning home, increased odds of discharge to a setting of higher dependency, and excess mortality independent of comorbidity, age, and sex. These findings emphasize the potentially devastating outcomes associated with delirium and highlight the need for timely diagnosis and hospital-wide management., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Progress in degenerative cervical myelopathy (DCM) is hindered by inconsistent measurement and reporting. This impedes data aggregation and outcome comparison across studies. This limitation can be reversed by developing a core measurement set (CMS) for DCM research. Previously, the AO Spine Research Objectives and Common Data Elements for DCM (AO Spine RECODE-DCM) defined 'what' should be measured in DCM: the next step of this initiative is to determine 'how' to measure these features. This protocol outlines the steps necessary for the development of a CMS for DCM research and audit., Methods and Analysis: The CMS will be developed in accordance with the guidance developed by the Core Outcome Measures in Effectiveness Trials and the Consensus-based Standards for the selection of health Measurement Instruments. The process involves five phases. In phase 1, the steering committee agreed on the constructs to be measured by sourcing consensus definitions from patients, professionals and the literature. In phases 2 and 3, systematic reviews were conducted to identify tools for each construct and aggregate their evidence. Constructs with and without tools were identified, and scoping reviews were conducted for constructs without tools. Evidence on measurement properties, as well as on timing of assessments, are currently being aggregated. These will be presented in phase 4: a consensus meeting where a multi-disciplinary panel of experts will select the instruments that will form the CMS. Following selection, guidance on the implementation of the CMS will be developed and disseminated (phase 5). A preliminary CMS review scheduled at 4 years from release., Ethics and Dissemination: Ethical approval was obtained from the University of Cambridge (HBREC2019.14). Dissemination strategies will include peer-reviewed scientific publications; conference presentations; podcasts; the identification of AO Spine RECODE-DCM ambassadors; and engagement with relevant journals, funders and the DCM community., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Walking over obstacles requires precise foot placement while maintaining balance control of the center of mass (CoM) and the flexibility to adapt the gait patterns. Most individuals with incomplete spinal cord injury (iSCI) are capable of overground walking on level ground; however, gait stability and adaptation may be compromised. CoM control was investigated during a challenging target walking (TW) task in individuals with iSCI compared to healthy controls. The hypothesis was that individuals with iSCI, when challenged with TW, show a lack of gait pattern adaptability which is reflected by an impaired adaptation of CoM movement compared to healthy controls., Methods: A single-center controlled diagnostic clinical trial with thirteen participants with iSCI (0.3-24 years post injury; one subacute and twelve chronic) and twelve healthy controls was conducted where foot and pelvis kinematics were acquired during two conditions: normal treadmill walking (NW) and visually guided target walking (TW) with handrail support, during which participants stepped onto projected virtual targets synchronized with the moving treadmill surface. Approximated CoM was calculated from pelvis markers and used to calculate CoM trajectory length and mean CoM Euclidean distance TW-NW (primary outcome). Nonparametric statistics, including spearman rank correlations, were performed to evaluate the relationship between clinical parameter, outdoor mobility score, performance, and CoM parameters (secondary outcome)., Results: Healthy controls adapted to TW by decreasing anterior-posterior and vertical CoM trajectory length (p < 0.001), whereas participants with iSCI reduced CoM trajectory length only in the vertical direction (p = 0.002). Mean CoM Euclidean distance TW-NW correlated with participants' neurological level of injury (R = 0.76, p = 0.002) and CoM trajectory length (during TW) correlated with outdoor mobility score (R = - 0.64, p = 0.026)., Conclusions: This study demonstrated that reduction of CoM movement is a common strategy to cope with TW challenge in controls, but it is impaired in individuals with iSCI. In the iSCI group, the ability to cope with gait challenges worsened the more rostral the level of injury. Thus, the TW task could be used as a gait challenge paradigm in ambulatory iSCI individuals. Trial registration Registry number/ ClinicalTrials.gov Identifier: NCT03343132, date of registration 2017/11/17., (© 2022. The Author(s).)

Study Design: Literature Review (Narrative)., Objective: To introduce the number one research priority for Degenerative Cervical Myelopathy (DCM): Raising Awareness., Methods: Raising awareness has been recognized by AO Spine RECODE-DCM as the number one research priority. This article reviews the evidence that awareness is low, the potential drivers, and why this must be addressed. Case studies of success from other diseases are also reviewed, drawing potential parallels and opportunities for DCM., Results: DCM may affect as many as 1 in 50 adults, yet few will receive a diagnosis and those that do will wait many years for it. This leads to poorer outcomes from surgery and greater disability. DCM is rarely featured in healthcare professional training programs and has received relatively little research funding (<2% of Amyotrophic Lateral Sclerosis or Multiple Sclerosis over the last 25 years). The transformation of stroke and acute coronary syndrome services, from a position of best supportive care with occasional surgery over 50 years ago, to avoidable disability today, represents transferable examples of success and potential opportunities for DCM. Central to this is raising awareness., Conclusion: Despite the devastating burden on the patient, recognition across research, clinical practice, and healthcare policy are limited. DCM represents a significant unmet need that must become an international public health priority.

Study Design: Literature Review (Narrative)., Objective: To propose a new framework, to support the investigation and understanding of the pathobiology of DCM, AO Spine RECODE-DCM research priority number 5., Methods: Degenerative cervical myelopathy is a common and disabling spinal cord disorder. In this perspective, we review key knowledge gaps between the clinical phenotype and our biological models. We then propose a reappraisal of the key driving forces behind DCM and an individual's susceptibility, including the proposal of a new framework., Results: Present pathobiological and mechanistic knowledge does not adequately explain the disease phenotype; why only a subset of patients with visualized cord compression show clinical myelopathy, and the amount of cord compression only weakly correlates with disability. We propose that DCM is better represented as a function of several interacting mechanical forces, such as shear, tension and compression, alongside an individual's vulnerability to spinal cord injury, influenced by factors such as age, genetics, their cardiovascular, gastrointestinal and nervous system status, and time., Conclusion: Understanding the disease pathobiology is a fundamental research priority. We believe a framework of mechanical stress, vulnerability, and time may better represent the disease as a whole. Whilst this remains theoretical, we hope that at the very least it will inspire new avenues of research that better encapsulate the full spectrum of disease.

Study Design: Narrative review., Objectives: To discuss the importance of establishing diagnostic criteria in Degenerative Cervical Myelopathy (DCM), including factors that must be taken into account and challenges that must be overcome in this process., Methods: Literature review summarising current evidence of establishing diagnostic criteria for DCM., Results: Degenerative Cervical Myelopathy (DCM) is characterised by a degenerative process of the cervical spine resulting in chronic spinal cord dysfunction and subsequent neurological disability. Diagnostic delays lead to progressive neurological decline with associated reduction in quality of life for patients. Surgical decompression may halt neurologic worsening and, in many cases, improves function. Therefore, making a prompt diagnosis of DCM in order to facilitate early surgical intervention is a clinical priority in DCM., Conclusion: There are often extensive delays in the diagnosis of DCM. Presently, no single set of diagnostic criteria exists for DCM, making it challenging for clinicians to make the diagnosis. Earlier diagnosis and subsequent specialist referral could lead to improved patient outcomes using existing treatment modalities.

Degenerative cervical myelopathy (DCM) is hallmarked by spinal canal narrowing and related cord compression and myelopathy. Cerebrospinal fluid (CSF) pressure dynamics are likely disturbed due to spinal canal stenosis. The study aimed to investigate the diagnostic value of continuous intraoperative CSF pressure monitoring during surgical decompression. This prospective single center study (NCT02170155) enrolled DCM patients who underwent surgical decompression between December 2019 and May 2021. Data from n  = 17 patients were analyzed and symptom severity graded with the modified Japanese Orthopedic Score (mJOA). CSF pulsations were continuously monitored with a lumbar intrathecal catheter during surgical decompression. Mean patient age was 62 ± 9 years (range 38-73; 8 female), symptoms were mild-moderate in most patients (mean mJOA 14 ± 2, range 10-18). Measurements were well tolerated without safety concerns. In 15/16 patients (94%), CSF pulsations increased at the time of surgical decompression. In one case, responsiveness could not be evaluated for technical reasons. Unexpected CSF pulsation decrease was related to adverse events (i.e., CSF leakage). Median CSF pulsation amplitudes increased from pre-decompression (0.52 mm Hg, interquartile range [IQR] 0.71) to post-decompression (0.72 mm Hg, IQR 0.96; p  = 0.001). Mean baseline CSF pressure increased with lower magnitude than pulsations, from 9.5 ± 3.5 to 10.3 ± 3.8 mm Hg ( p  = 0.003). Systematic relations of CSF pulsations were confined to surgical decompression, independent of arterial blood pressure ( p  = 0.927) or heart rate ( p  = 0.102). Intraoperative CSF pulsation monitoring was related to surgical decompression while in addition adverse events could be discerned. Further investigation of the clinical value of intraoperative guidance for decompression in complex DCM surgery is promising.

Objectives: To evaluate the measurement properties of outcome measures currently used in the assessment of degenerative cervical myelopathy (DCM) for clinical research., Design: Systematic review DATA SOURCES: MEDLINE and EMBASE were searched through 4 August 2020., Eligibility Criteria: Primary clinical research published in English and whose primary purpose was to evaluate the measurement properties or clinically important differences of instruments used in DCM., Data Extraction and Synthesis: Psychometric properties and clinically important differences were both extracted from each study, assessed for risk of bias and presented in accordance with the Consensus-based Standards for the selection of health Measurement Instruments criteria., Results: Twenty-nine outcome instruments were identified from 52 studies published between 1999 and 2020. They measured neuromuscular function (16 instruments), life impact (five instruments), pain (five instruments) and radiological scoring (five instruments). No instrument had evaluations for all 10 measurement properties and <50% had assessments for all three domains (ie, reliability, validity and responsiveness). There was a paucity of high-quality evidence. Notably, there were no studies that reported on structural validity and no high-quality evidence that discussed content validity. In this context, we identified nine instruments that are interpretable by clinicians: the arm and neck pain scores; the 12-item and 36-item short form health surveys; the Japanese Orthopaedic Association (JOA) score, modified JOA and JOA Cervical Myelopathy Evaluation Questionnaire; the neck disability index; and the visual analogue scale for pain. These include six scores with barriers to application and one score with insufficient criterion and construct validity., Conclusions: This review aggregates studies evaluating outcome measures used to assess patients with DCM. Overall, there is a need for a set of agreed tools to measure outcomes in DCM. These findings will be used to inform the development of a core measurement set as part of AO Spine RECODE-DCM., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Degenerative cervical myelopathy (DCM) is a common non-traumatic spinal cord disorder and characterized by progressive neurological impairment. Generally, it is still underdiagnosed and referral to spine specialists is often late, when patients already present with incomplete cervical spinal cord injury (SCI). To improve early diagnosis and accelerate referral, diagnostic criteria for DCM are required. Recently, AO Spine RECODE- DCM (REsearch Objectives and Common Data Elements for Degenerative Cervical Myelopathy) (aospine.org/recode), an international, interdisciplinary and interprofessional initiative, including patients with DCM, was funded with the aim to accelerate knowledge discovery that can change outcomes. In this perspective we advocate for the participation of SCI specialists in this process, where the expertise and perspective on this disorder and requirements for the diagnostic and therapeutic work up is well developed., (© 2021. The Author(s).)

Background and Purpose: Delirium is a common severe complication of stroke. We aimed to determine the cost-of-illness and risk factors of poststroke delirium (PSD)., Methods: This prospective single-center study included n=567 patients with acute stroke from a hospital-wide delirium cohort study and the Swiss Stroke Registry in 2014. Delirium was determined by Delirium Observation Screening Scale or Intensive Care Delirium Screening Checklist 3 times daily during the first 3 days of admission. Costs reflected the case-mix index and diagnosis-related groups from 2014 and were divided into nursing, physician, and total costs. Factors associated with PSD were assessed with multiple regression analysis. Partial correlations and quantile regression were performed to assess costs and other factors associated with PSD., Results: The incidence of PSD was 39.0% (221/567). Patients with delirium were older than non-PSD (median 76 versus 70 years; P<0.001), 52% male (115/221) versus 62% non-PSD (214/346) and hospitalized longer (mean 11.5 versus 9.3 days; P<0.001). Dementia was the most relevant predisposing factor for PSD (odds ratio, 16.02 [2.83–90.69], P=0.002). Moderate to severe stroke (National Institutes of Health Stroke Scale score 16–20) was the most relevant precipitating factor (odds ratio, 36.10 [8.15–159.79], P<0.001). PSD was a strong predictor for 3-month mortality (odds ratio, 15.11 [3.33–68.53], P<0.001). Nursing and total costs were nearly twice as high in PSD (P<0.001). There was a positive correlation between total costs and admission National Institutes of Health Stroke Scale (correlation coefficient, 0.491; P<0.001) and length of stay (correlation coefficient, 0.787; P<0.001) in all patients. Quantile regression revealed rising nursing and total costs associated with PSD, higher National Institutes of Health Stroke Scale, and longer hospital stay (all P<0.05)., Conclusions: PSD was associated with greater stroke severity, prolonged hospitalization, and increased nursing and total costs. In patients with severe stroke, dementia, or seizures, PSD is anticipated, and additional costs are associated with hospitalization.

Aim: Although the risk factors for delirium in general medicine are well-established, their significance in cardiac diseases remains to be determined. Therefore, we evaluated the predisposing and precipitating risk factors in patients hospitalized with acute and chronic heart disease. Methods and Results: In this observational cohort study, 1,042 elderly patients (≥65 years) admitted to cardiology wards, 167 with and 875 without delirium, were included. The relevant sociodemographic and cardiac- and medical-related clusters were assessed by simple and multiple regression analyses and prediction models evaluating their association with delirium. The prevalence of delirium was 16.0%. The delirious patients were older (mean 80 vs. 76 years; p < 0.001) and more often institutionalized prior to admission (3.6 vs. 1.4%, p = 0.05), hospitalized twice as long (12 ± 10 days vs. 7 ± 7 days; p < 0.001), and discharged more often to nursing homes (4.8 vs. 0.6%, p < 0.001) or deceased (OR, 2.99; 95% CI, 1.53-5.85; p = 0.003). The most relevant risk factor was dementia (OR, 18.11; 95% CI, 5.77-56.83; p < 0.001), followed by history of stroke (OR, 6.61; 95% CI 1.35-32.44; p = 0.020), and pressure ulcers (OR, 3.62; 95% CI, 1.06-12.35; p = 0.040). The predicted probability for developing delirium was highest in patients with reduced mobility and institutionalization prior to admission (PP = 31.2%, p = 0.001). Of the cardiac diseases, only valvular heart disease (OR, 1.57; 95% CI, 1.01-2.44; p = 0.044) significantly predicted delirium. The patients undergoing cardiac interventions did not have higher rates of delirium (OR, 1.39; 95% CI 0.91-2.12; p = 0.124). Conclusion: In patients admitted to a cardiology ward, age-related functional and cognitive impairment, history of stroke, and pressure ulcers were the most relevant risk factors for delirium. With regards to specific cardiological factors, only valvular heart disease was associated with risk for delirium. Knowing these factors can help cardiologists to facilitate the early detection and management of delirium., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zipser, Hildenbrand, Haubner, Deuel, Ernst, Petry, Schubert, Jordan, von Känel and Boettger.)

Objective: Synaptopathy including alterations of synaptic plasticity (long-term potentiation, LTP) may precede neurodegeneration in Alzheimer's disease (AD). We studied LTP-like corticospinal plasticity induced by paired-associative stimulation (PAS LTP ) in AD and its prodromal stage, amnestic mild cognitive impairment (aMCI)., Methods: 15 AD and 15 aMCI patients, and 23 demographically matched healthy controls (HC) were included. Resting motor threshold (RMT) and stimulus intensity needed to evoke motor evoked potentials (MEP) of 1 mV (SI1mV) were obtained as single-pulse transcranial magnetic stimulation (TMS) measures of corticospinal excitability in a hand muscle at baseline, followed by PAS LTP using standard methodology. MEP amplitude change after PAS LTP normalized to baseline was defined as plasticity effect. All measures were repeated in two visits for examining test-retest reliability., Results: SI1mV were lower in aMCI compared to HC, while there was no difference between AD and HC. RMT and SI1mV showed excellent test-retest reliability in all groups. PAS LTP indiscriminately did not induce LTP-like plasticity in any of the groups, and expressed poor test-retest reliability., Conclusions: aMCI shows corticospinal hyperexcitability, consistent with glutamatergic excitotoxicity in early-stage AD. Possible abnormalities of LTP-like plasticity could not be reliably tested with the standard PAS LTP protocol due to massive inter-subject variability even in HC, and poor test-retest reliability., Significance: Findings indicate corticospinal hyperexcitability in prodromal AD, and reliability of single-pulse TMS measures for identifying such abnormality. In contrast, the standard PAS LTP protocol may not be suitable for assessing LTP-like motor cortical plasticity, given its overall nil effect and poor test-retest reliability., Competing Interests: Declaration of Competing Interest A.M. D.D, P.S., C.L., O.P. and C.Z. report no conflicts of interest. U.Z. has received a grant from Janssen Pharmaceutica NV to support conduction of this work. In addition, he has received grants from European Research Council (ERC), German Research Foundation (DFG), German Federal Ministry of Education and Research (BMBF), Bristol Myers Squibb, Servier, Biogen Idec GmbH, and personal fees from Bayer Vital GmbH, Pfizer GmbH, CorTec GmbH, all not related to this work. I.L.-S. has received grants from Janssen Pharmaceutica NV, Michael J Fox Foundation, National Center of Excellence in Research, Luxembourg National Research Fund, European Commission Horizon 2020, International Parkinson Fonds GmbH IPO, all outside the submitted work. D.B. has received grants from Janssen Pharmaceutica NV, German Parkinson’s Disease Association (dPV), BMWi, BMBF, Parkinson Fonds Deutschland gGmbH, UCB Pharma GmbH, EU, Novartis Pharma GmbH, Lundbeck, Damp foundation, and personal fees from Biogen, BIAL, Lundbeck, UCB Pharma GmbH, AbbVie, Biogen, BIAL, Lundbeck, UCB Pharma GmbH Zambon, Desitin, GE, all not related to this work. G.S., K.T., and M.T. are employees of Janssen Research & Development, LLC or Janssen Research and Development, a division of Janssen Pharmaceutica NV, and hold stock/stock options in the company (Johnson & Johnson). G.S., K.T., and M.T. have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in the subject matter or materials discussed in the manuscript apart from those disclosed., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objectives: Patients with terminal illness are at high risk of developing delirium, in particular, those with multiple predisposing and precipitating risk factors. Delirium in palliative care is largely under-researched, and few studies have systematically assessed key aspects of delirium in elderly, palliative-care patients., Methods: In this prospective, observational cohort study at a tertiary care center, 229 delirious palliative-care patients stratified by age: <65 (N = 105) and ≥65 years (N = 124), were analyzed with logistic regression models to identify associations with respect to predisposing and precipitating factors., Results: In 88% of the patients, the underlying diagnosis was cancer. Mortality rate and median time to death did not differ significantly between the two age groups. No inter-group differences were detected with respect to gender, care requirements, length of hospital stay, or medical costs. In patients ≥65 years, exclusively predisposing factors were relevant for delirium, including hearing impairment [odds ratio (OR) 3.64; confidence interval (CI) 1.90-6.99; P < 0.001], hypertension (OR 3.57; CI 1.84-6.92; P < 0.001), and chronic kidney disease (OR 4.84; CI 1.19-19.72; P = 0.028). In contrast, in patients <65 years, only precipitating factors were relevant for delirium, including cerebral edema (OR 0.02; CI 0.01-0.43; P = 0.012)., Significance of Results: The results of this study demonstrate that death in delirious palliative-care patients occurs irrespective of age. The multifactorial nature and adverse outcomes of delirium across all age in these patients require clinical recognition. Potentially reversible factors should be detected early to prevent or mitigate delirium and its poor survival outcomes.

Objective: Delirium is a frequent complication in advanced cancer patients, among whom it is frequently underdiagnosed and inadequately treated. To date, evidence on risk factors and the prognostic impact of delirium on outcomes remains sparse in this patient population., Method: In this prospective observational cohort study at a single tertiary-care center, 1,350 cancer patients were enrolled. Simple and multiple logistic regression models were utilized to identify associations between predisposing and precipitating factors and delirium. Cox proportional-hazards models were used to estimate the effect of delirium on death rate., Results: In our patient cohort, the prevalence of delirium was 34.3%. Delirium was associated inter alia with prolonged hospitalization, a doubling of care requirements, increased healthcare costs, increased need for institutionalization (OR 3.22), and increased mortality (OR 8.78). Predisposing factors for delirium were impaired activity (OR 10.82), frailty (OR 4.75); hearing (OR 2.23) and visual impairment (OR 1.89), chronic pneumonitis (OR 2.62), hypertension (OR 1.46), and renal insufficiency (OR 1.82). Precipitating factors were acute renal failure (OR 7.50), pressure sores (OR 3.78), pain (OR 2.86), and cystitis (OR 1.32). On multivariate Cox regression, delirium increased the mortality risk sixfold (HR 5.66). Age ≥ 65 years and comorbidities further doubled the mortality risk of delirious patients (HR 1.77; HR 2.05)., Significance of Results: Delirium is common in cancer patients and associated with increased morbidity and mortality. Systematically categorizing predisposing and precipitating factors might yield new strategies for preventing and managing delirium in cancer patients.

Objective: The prevalence rates and adversities of delirium have not yet been systematically evaluated and are based on selected populations, limited sample sizes, and pooled studies. Therefore, this study assesses the prevalence rates and outcome of and odds ratios for managing services for delirium., Methods: In this prospective cohort study, based on the Diagnostic and Statistical Manual (DSM) 5, the Delirium Observation Screening (DOS) scale, and the Intensive Care Delirium Screening Checklist (ICDSC) construct, 28,118 patients from 35 managing services were included, and the prevalence rates and adverse outcomes were determined by simple logistic regressions and their corresponding odds ratios (ORs)., Results: Delirious patients were older, admitted from institutions (OR 3.44-5.2), admitted as emergencies (OR 1.87), hospitalized twice longer, and discharged, transferred to institutions (OR 5.47-6.6) rather than home (OR 0.1), or deceased (OR 43.88). The rate of undiagnosed delirium was 84.2%. The highest prevalence rates were recorded in the intensive care units (47.1-84.2%, pooled 67.9%); in the majority of medical services, rates ranged from 20% to 40% (pooled 26.2%), except, at both ends, palliative care (55.9%), endocrinology (8%), and rheumatology (4.4%). Conversely, in surgery and its related services, prevalence rates were lower (pooled 13.1%), except for cardio- and neurosurgical services (53.3% and 46.4%); the lowest prevalence rate was recorded in obstetrics (2%)., Significance of Results: Delirium remains underdiagnosed, and novel screening approaches are required. Furthermore, this study identified the impact of delirium on patients, determined the prevalence rates for 32 services, and elucidated the association between individual services and delirium.

Background and Purpose: The spinal cord is subject to a periodic, cardiac-related movement, which is increased at the level of a cervical stenosis. Increased oscillations may exert mechanical stress on spinal cord tissue causing intramedullary damage. Motion analysis thus holds promise as a biomarker related to disease progression in degenerative cervical myelopathy. Our aim was characterization of the cervical spinal cord motion in patients with degenerative cervical myelopathy., Materials and Methods: Phase-contrast MR imaging data were analyzed in 55 patients (37 men; mean age, 56.2 [SD,12.0] years; 36 multisegmental stenoses) and 18 controls (9 men, P  = .368; mean age, 62.2 [SD, 6.5] years; P  = .024). Parameters of interest included the displacement and motion pattern. Motion data were pooled on the segmental level for comparison between groups., Results: In patients, mean craniocaudal oscillations were increased manifold at any level of a cervical stenosis (eg, C5 displacement: controls [ n  = 18], 0.54 [SD, 0.16] mm; patients [ n  = 29], monosegmental stenosis [ n  = 10], 1.86 [SD, 0.92] mm; P  < .001) and even in segments remote from the level of the stenosis (eg, C2 displacement: controls [ n  = 18], 0.36 [SD, 0.09] mm; patients [ n  = 52]; stenosis: C3, n  = 21; C4, n  = 11; C5, n  = 18; C6, n  = 2; 0.85 [SD, 0.46] mm; P  < .001). Motion at C2 differed with the distance to the next stenotic segment and the number of stenotic segments. The motion pattern in most patients showed continuous spinal cord motion throughout the cardiac cycle., Conclusions: Patients with degenerative cervical myelopathy show altered spinal cord motion with increased and ongoing oscillations at and also beyond the focal level of stenosis. Phase-contrast MR imaging has promise as a biomarker to reveal mechanical stress to the cord and may be applicable to predict disease progression and the impact of surgical interventions., (© 2021 by American Journal of Neuroradiology.)

Objective: To evaluate the relationship between circulating phenylalanine and brain function as well as neuropsychiatric symptoms in adults with phenylketonuria., Methods: In this prospective cross-sectional study, early-treated patients with phenylketonuria older than 30 years and age- and sex-matched controls were included. Extensive neurologic evaluation, neuropsychological and behavioral testing, sensory and motor evoked potentials, and MRI were performed. CSF concentrations of neurodegenerative markers were evaluated in addition in a subset of 10 patients., Results: Nineteen patients with phenylketonuria (median age 41 years) with different phenylalanine levels (median 873 μmol/L) entered the study. They showed higher prevalence of neurologic symptoms, cognitive and behavioral abnormalities, autonomic dysfunction, alterations in neurophysiologic measures, and atrophy in putamen and right thalamus compared to controls. In CSF, patients with phenylketonuria exhibited higher β-amyloid 1-42 ( p = 0.003), total tau ( p < 0.001), and phosphorylated tau ( p = 0.032) levels compared to controls. Plasma phenylalanine levels highly correlated with the number of failed neuropsychological tests ( r = 0.64, p = 0.003), neuropsychiatric symptoms ( r = 0.73, p < 001), motor evoked potential latency ( r = 0.48, p = 0.030), and parietal lobe atrophy., Conclusions: Our study provides strong evidence for a correlation between phenylalanine levels and clinical, neuropsychological, neurophysiologic, biochemical, and imaging alterations in adult patients with phenylketonuria., (© 2020 American Academy of Neurology.)

Introduction: Degenerative cervical myelopathy (DCM) leads to functional impairment by compression of the spinal cord and nerve roots. In DCM, the dynamics of cerebrospinal fluid pressure (CSFP) and intraspinal pressure (ISP), as well as spinal cord perfusion pressure (SCPP) remain not investigated yet. Recent technical advances have enabled investigation of these parameters in acute spinal cord injury (SCI). We aim to investigate the properties of CSFP/ISP and spinal cord hemodynamics during and after decompressive surgery in DCM., Materials and Methods: Four patients with DCM were enrolled; during surgery and 24 h postoperative, ISP at level was measured in one patient, and CSFP was measured in two patients. In one patient, CSFP was recorded at bedside before surgery., Results: All measurements were conducted without adverse events and were well tolerated. With CSFP analysis, post-decompression Queckenstedt's test was responsive in two patients (i.e., jugular vein compression resulted in an elevation of CSFP pressure). In the patient whose CSFP was tested at bedside, Queckenstedt's test was not responsive before decompression. Individual optimum SCPPs were calculated to be between 70 and 75 mmHg., Conclusion: ISP and CSFP can reflect spinal compression and sufficient decompression. A better understanding and systematic monitoring possibly lead to improved hemodynamic management and may allow early recognition of postoperative complications such as swelling and bleeding.

Introduction: Degenerative cervical myelopathy (DCM) is a disabling spinal disorder characterised by sensorimotor deficits of upper and lower limbs, neurogenic bladder dysfunction and neuropathic pain. When suspected, cervical MRI helps to reveal spinal cord compression and rules out alternative diagnoses. However, the correlation between radiological findings and symptoms is weak. Cerebrospinal fluid pressure (CSFP) analysis may complement the appreciation of cord compression and be used for intraoperative and postoperative monitorings in patients undergoing surgical decompression., Methods and Analysis: Twenty patients diagnosed with DCM undergoing surgical decompression will receive standardised lumbar CSFP monitoring immediately before, during and 24 hours after operation. Rest (ie, opening pressure, CSF pulsation) and stimulated (ie, Valsalva, Queckenstedt's) CSFP-findings in DCM will be compared with 20 controls and results from CSFP monitoring will be related to clinical and neurophysiological findings. Arterial blood pressure will be recorded perioperatively and postoperatively to calculate spinal cord perfusion pressure and spinal vascular reactivity index. Furthermore, measures of CSFP will be compared with markers of spinal cord compression by means of MR imaging., Ethics and Dissemination: The study protocol conformed to the latest revision of the Declaration of Helsinki and was approved by the local Ethics Committee of the University Hospital of Zurich (KEK-ZH number PB-2016-00623). The main publications from this study will cover the CSFP fluid dynamics and pressure analysis preoperative, perioperative and postoperative correlated with imaging, clinical scores and neurophysiology. Other publications will deal with preoperative and postoperative spinal perfusion. Furthermore, we will disseminate an analysis on waveform morphology and the correlation with blood pressure and ECG. Parts of the data will be used for computational modelling of cervical stenosis., Trial Registration Number: ClinicalTrials.gov Registry (NCT02170155)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The hypoactive, hyperactive, and mixed subtypes of delirium differently impact patient management and prognosis, yet the evidence remains sparse. Therefore, we examined the outcome of varying management strategies in the subtypes of delirium., Methods: In this observational cohort study, 602 patients were managed for delirium over 20 days with the following strategies: supportive care alone or in combination with psychotropics, single, dual, or triple+ psychotropic regimens. Cox regression models were calculated for time to remission and benefit rates (BRs) of management strategies., Results: Generally, the mixed subtype of delirium caused more severe and persistent delirium, and the hypoactive subtype was more persistent than the hyperactive subtype. The subtypes of delirium were similarly predictive for mortality (P = 0.697) and transfer to inpatient psychiatric care (P = 0.320). In the mixed subtype, overall, psychotropic drugs were administered more often (P = 0.016), and particularly triple+ regimens were administered more commonly compared to hypoactive delirium (P = 0.007). Patients on supportive care benefited most, whereas those on triple+ regimens did worst in terms of remission in all groups of hypoactive, hyperactive, and mixed subtypes (BR: 4.59, CI 2.01-10.48; BR: 4.59, CI 1.76-31.66; BR: 3.36, CI 1.73-6.52; all P < 0.05)., Significance of Results: The mixed subtype was more persistent to management than the hypoactive and hyperactive subtypes. Delirium management remains controversial and, generally, supportive care benefited patients most. Psychopharmacological management for delirium requires careful choosing of and limiting the number of psychotropics.

Introduction: Predisposing and precipitating factors for delirium are well known; however, their interaction and impact on delirium in neurological patients remains largely unknown. Therefore, those factors were evaluated in hospitalized patients with neurological disorders., Methods: In this prospective cohort study, 1487 neurological patients were included, 356 patients with delirium and 1131 without delirium. Relevant neurological- and medical-related clusters were assessed with multiple regression analyses, prediction models, and cluster analysis evaluating their association with delirium., Results: The 1-year incidence of delirium in this cohort was 23.9%. Delirium developed in 31% of patients with stroke, in 39.5% with epilepsy, and in 58.4% with ICH. The most relevant predisposing factors were substance-use disorders (OR 4.24, 2.28-7.78, p < 0.001), advanced age (OR 3.44, CI 2.40-4.92, p < 0.001), and neurodegenerative disorders (OR 2.58, CI 1.47-4.54, p = 0.001). The most relevant precipitating factors were meningitis (OR 21.52, CI 1.22-379.83, p = 0.036), acute renal failure (OR 10.01, CI 1.13-88.73, p = 0.039), and intracranial hemorrhage (OR 3.62, CI 2.08-6.30, p < 0.001). Delirious patients were hospitalized 6 days longer, had higher in-hospital mortality, and were discharged more often to nursing homes and rehabilitation. Best predictor for delirium was the coexistence of advanced age with epilepsy (58.3%, p < 0.001), while patients aged < 65 years without epilepsy and stroke rarely developed delirium (5.1%, p < 0.001)., Conclusions: Delirium is common in elder neurological patients and associated with worse outcome. Primary cerebral conditions most frequently precipitate delirium in neurology. Neurologists are advised to monitor symptoms of delirium in the presence of risk factors to enable both timely diagnostic work-up and management of delirium.