Influence of age on the relation between body position and noninvasively acquired intracranial pulse waves.

The capacitive measurement of the head's dielectric properties has been recently proposed as a noninvasive method for deriving surrogates of craniospinal compliance (CC), a parameter used in the evaluation of space-occupying neurological disorders. With the higher prevalence of such disorders in the older compared to the younger population, data on the head's dielectric properties of older healthy individuals would be of particularly high value before assessing pathologic changes. However, so far only measurements on young volunteers (< 30 years) were reported. In the present study, we have investigated the capacitively obtained electric signal known as W in older healthy individuals. Thirteen healthy subjects aged > 60 years were included in the study. W was acquired in the resting state (supine horizontal position), and during head-up and head-down tilting. AMP, the peak-to-valley amplitude of W related to cardiac action, was extracted from W. AMP was higher in this older cohort compared to the previously investigated younger one (0°: 5965 ± 1677 arbitrary units (au)). During head-up tilting, AMP decreased (+ 60°: 4446 ± 1620 au, P < 0.001), whereas it increased during head-down tilting (- 30°: 7600 ± 2123 au, P < 0.001), as also observed in the younger cohort. Our observation that AMP, a metric potentially reflective of CC, is higher in the older compared to the younger cohort aligns with the expected decrease of CC with age. Furthermore, the robustness of AMP is reinforced by the consistent relative changes observed during tilt testing in both cohorts.

Scoping Review with Topic Modeling on the Diagnostic Criteria for Degenerative Cervical Myelopathy.

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.

The Frequency of Symptoms in Patients With a Diagnosis of Degenerative Cervical Myelopathy: Results of a Scoping Review.

STUDY DESIGN: Delayed diagnosis of degenerative cervical myelopathy (DCM) is associated with reduced quality of life and greater disability. Developing diagnostic criteria for DCM has been identified as a top research priority. OBJECTIVES: This scoping review aims to address the following questions: What is the diagnostic accuracy and frequency of clinical symptoms in patients with DCM? METHODS: A scoping review was conducted using a database of all primary DCM studies published between 2005 and 2020. Studies were included if they (i) assessed the diagnostic accuracy of a symptom using an appropriate control group or (ii) reported the frequency of a symptom in a cohort of DCM patients. RESULTS: This review identified three studies that discussed the diagnostic accuracy of various symptoms and included a control group. An additional 58 reported on the frequency of symptoms in a cohort of patients with DCM. The most frequent and sensitive symptoms in DCM include unspecified paresthesias (86%), hand numbness (82%) and hand paresthesias (79%). Neck and/or shoulder pain was present in 51% of patients with DCM, whereas a minority had back (19%) or lower extremity pain (10%). Bladder dysfunction was uncommon (38%) although more frequent than bowel (23%) and sexual impairment (4%). Gait impairment is also commonly seen in patients with DCM (72%). CONCLUSION: Patients with DCM present with many different symptoms, most commonly sensorimotor impairment of the upper extremities, pain, bladder dysfunction and gait disturbance. If patients present with a combination of these symptoms, further neuroimaging is indicated to confirm the diagnosis of DCM.

The value of Clinical signs in the diagnosis of Degenerative Cervical Myelopathy - A Systematic review and Meta-analysis.

STUDY DESIGN: Delayed diagnosis of degenerative cervical myelopathy (DCM) is likely due to a combination of its subtle symptoms, incomplete neurological assessments by clinicians and a lack of public and professional awareness. Diagnostic criteria for DCM will likely facilitate earlier referral for definitive management. OBJECTIVES: This systematic review aims to determine (i) the diagnostic accuracy of various clinical signs and (ii) the association between clinical signs and disease severity in DCM? METHODS: A search was performed to identify studies on adult patients that evaluated the diagnostic accuracy of a clinical sign used for diagnosing DCM. Studies were also included if they assessed the association between the presence of a clinical sign and disease severity. The QUADAS-2 tool was used to evaluate the risk of bias of individual studies. RESULTS: This review identified eleven studies that used a control group to evaluate the diagnostic accuracy of various signs. An additional 61 articles reported on the frequency of clinical signs in a cohort of DCM patients. The most sensitive clinical tests for diagnosing DCM were the Tromner and hyperreflexia, whereas the most specific tests were the Babinski, Tromner, clonus and inverted supinator sign. Five studies evaluated the association between the presence of various clinical signs and disease severity. There was no definite association between Hoffmann sign, Babinski sign or hyperreflexia and disease severity. CONCLUSION: The presence of clinical signs suggesting spinal cord compression should encourage health care professionals to pursue further investigation, such as neuroimaging to either confirm or refute a diagnosis of DCM.

Queckenstedt's test repurposed for the quantitative assessment of the cerebrospinal fluid pulsatility curve.

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.

Cerebrospinal Fluid Pressure Dynamics as a Bedside Test in Traumatic Spinal Cord Injury to Assess Surgical Spinal Cord Decompression: Safety, Feasibility, and Proof-of-Concept.

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.

The effect of body position change on noninvasively acquired intracranial pulse waves.

Objective. Craniospinal compliance (CC) is an important metric for the characterization of space-occupying neurological pathologies. CC is obtained using invasive procedures that carry risks for the patients. Therefore, noninvasive methods for acquiring surrogates of CC have been proposed, most recently based on changes in the head's dielectric properties during the cardiac cycle. Here, we have tested whether changes in body position, which are known to influence CC, are reflected in a capacitively acquired signal (hereinafter referred to as W) originating from dynamic changes of the head's dielectric properties.Approach. eighteen young healthy volunteers were included in the study. After 10 min in supine position, subjects were tilted head-up (HUT), back to 0° (horizontal, control), and then head-down (HDT). Metrics related to cardiovascular action were extracted from W, including AMP, the peak-to-valley amplitude of the cardiac modulation of W. Computational electromagnetic simulations were performed to probe the association between intracranial volume change and W.Main results. AMP decreased during HUT (0°: 2869 ± 597 arbitrary units (au); +75°: 2307 ± 490 au,P= 0.002) and increased during HDT (-30°: 4403 ± 1428 au,P< 0.0001). The same behavior was predicted by the electromagnetic model.Significance. tilting affects the distribution of CC between cranial and spinal compartments. Cardiovascular action induces compliance-dependent oscillatory changes in the intracranial fluid composition, which causes corresponding variations in the head's dielectric properties. These manifest as increasing AMP with decreasing intracranial compliance, which suggests that W may contain information related to CC, and that it might be possible to derive CC surrogates therefrom.

Noninvasive Monitoring of Intracranial Pulse Waves.

OBJECTIVE: The clinical management of several neurological disorders benefits from the assessment of intracranial pressure and craniospinal compliance. However, the associated procedures are invasive in nature. Here, we aimed to assess whether naturally occurring periodic changes in the dielectric properties of the head could serve as the basis for deriving surrogates of craniospinal compliance noninvasively. METHODS: We designed a device and electrodes for noninvasive measurement of periodic changes of the dielectric properties of the human head. We characterized the properties of the device-electrode-head system by measurements on healthy volunteers, by computational modeling, and by electromechanical modeling. We then performed hyperventilation testing to assess whether the measured signal is of intracranial origin. RESULTS: Signals obtained with the device on volunteers showed characteristic cardiac and respiratory modulations. Signal oscillations can be attributed primarily to changes in resistive properties of the head during cardiac and respiratory cycles. Reduction of end-tidal CO2, through hyperventilation, resulted in a decrease in the signal amplitude associated with cardiovascular action. CONCLUSION: Given the higher CO2 reactivity of intracranial vessels compared to extracranial ones, the results of hyperventilation testing suggest that the acquired signal is, in part, of intracranial origin. SIGNIFICANCE: If confirmed in larger cohorts, our observations suggest that noninvasive capacitive acquisition of changes in the dielectric properties of the head could be used to derive surrogates of craniospinal compliance.

Theory for a non-invasive diagnostic biomarker for craniospinal diseases.

Monitoring intracranial pressure (ICP) and craniospinal compliance (CC) is frequently required in the treatment of patients suffering from craniospinal diseases. However, current approaches are invasive and cannot provide continuous monitoring of CC. Dynamic exchange of blood and cerebrospinal fluid (CSF) between cranial and spinal compartments due to cardiac action transiently modulates the geometry and dielectric properties of the brain. The resulting impedance changes can be measured and might be usable as a non-invasive CC surrogate. A numerically robust and computationally efficient approach based on the reciprocity theorem was developed to compute dynamic impedance changes resulting from small geometry and material property changes. The approach was successfully verified against semi-analytical benchmarks, before being combined with experimental brain pulsation data to study the information content of the impedance variation. The results indicate that the measurable signal is dominated by the pulsatile displacement of the cortical brain surface, with minor contributions from the ventricular surfaces and from changes in brain perfusion. Different electrode setups result in complementary information. The information content from the investigated three electrode pairs was employed to successfully infer subject-specific brain pulsation and motion features. This suggests that non-invasive CC surrogates based on impedance monitoring could be established.

Cerebrospinal fluid pressure dynamics reveal signs of effective spinal canal narrowing in ambiguous spine conditions.

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.

Insights Into the Low Rate of In-Pump Thrombosis With the HeartMate 3: Does the Artificial Pulse Improve Washout?

While earlier studies reported no relevant effect of the HeartMate 3 (HM3) artificial pulse (AP) on bulk pump washout, its effect on regions with prolonged residence times remains unexplored. Using numerical simulations, we compared pump washout in the HM3 with and without AP with a focus on the clearance of the last 5% of the pump volume. Results were examined in terms of flush-volume (V f , number of times the pump was flushed with new blood) to probe the effect of the AP independent of changing flow rate. Irrespective of the flow condition, the HM3 washout scaled linearly with flush volume up to 70% washout and slowed down for the last 30%. Flush volumes needed to washout 95% of the pump were comparable with and without the AP (1.3-1.4 V f ), while 99% washout required 2.1-2.2 V f with the AP vs. 2.5 V f without the AP. The AP enhanced washout of the bend relief and near-wall regions. It also transiently shifted or eliminated stagnation regions and led to rapid wall shear stress fluctuations below the rotor and in the secondary flow path. Our results suggest potential benefits of the AP for clearance of fluid regions that might elicit in-pump thrombosis and provide possible mechanistic rationale behind clinical data showing very low rate of in-pump thrombosis with the HM3. Further optimization of the AP sequence is warranted to balance washout efficacy while limiting blood damage.

Intraoperative Monitoring of CSF Pressure in Patients with Degenerative Cervical Myelopathy (COMP-CORD Study): A Prospective Cohort Study.

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.

Thrombotic Risk of Rotor Speed Modulation Regimes of Contemporary Centrifugal Continuous-flow Left Ventricular Assist Devices.

Contemporary centrifugal continuous-flow left ventricular assist devices (LVADs) incorporate dynamic speed modulation algorithms. Hemocompatibility of these periodic unsteady pump operating conditions has been only partially explored. We evaluated whether speed modulation induces flow alterations associated with detrimental prothrombotic effects. For this aim, we evaluated the thrombogenic profile of the HeartWare ventricular assist device (HVAD) Lavare Cycle (LC) and HeartMate3 (HM3) artificial pulse (AP) via comprehensive numerical evaluation of (i) pump washout, (ii) stagnation zones, (iii) shear stress regimens, and (iv) modeling of platelet activation status via the platelet activity state (PAS) model. Data were compared between different simulated operating scenarios, including: (i) constant rotational speed and pump pressure head, used as reference; (ii) unsteady pump pressure head as induced by cardiac pulsatility; and (iii) unsteady rotor speed modulation of the LC (HVAD) and AP (HM3). Our results show that pump washout did not improve across the different simulated scenarios in neither the HVAD nor the HM3. The LC reduced but did not eliminate flow stagnation (-57%) and did not impact metrics of HVAD platelet activation (median PAS: +0.4%). The AP reduced HM3 flow stagnation by up to 91% but increased prothrombotic shear stress and simulated platelet activation (median PAS: +124%). Our study advances understanding of the pathogenesis of LVAD thrombosis, suggesting mechanistic implications of rotor speed modulation. Our data provide rationale criteria for the future design optimization of next generation LVADs to further reduce hemocompatibility-related adverse events.