Gait pattern analysis in the home environment as a key factor for the reliable assessment of shunt responsiveness in patients with idiopathic normal pressure hydrocephalus

BackgroundThe identification of patients with gait disturbance associated with idiopathic normal pressure hydrocephalus (iNPH) is challenging. This is due to the multifactorial causes of gait disturbance in elderly people and the single moment examination of laboratory tests.ObjectiveWe aimed to assess whether the use of gait sensors in a patient's home environment could help establish a reliable diagnostic tool to identify patients with iNPH by differentiating them from elderly healthy controls (EHC).MethodsFive wearable inertial measurement units were used in 11 patients with iNPH and 20 matched EHCs. Data were collected in the home environment for 72 h. Fifteen spatio-temporal gait parameters were analyzed. Patients were examined preoperatively and postoperatively. We performed an iNPH sub-group analysis to assess differences between responders vs. non-responders. We aimed to identify parameters that are able to predict a reliable response to VP-shunt placement.ResultsNine gait parameters significantly differ between EHC and patients with iNPH preoperatively. Postoperatively, patients with iNPH showed an improvement in the swing phase (p = 0.042), and compared to the EHC group, there was no significant difference regarding the cadence and traveled arm distance. Patients with a good VP-shunt response (NPH recovery rate of ≥5) significantly differ from the non-responders regarding cycle time, cycle time deviation, number of steps, gait velocity, straight length, stance phase, and stance to swing ratio. A receiver operating characteristic analysis showed good sensitivity for a preoperative stride length of ≥0.44 m and gait velocity of ≥0.39 m/s.ConclusionThere was a significant difference in 60% of the analyzed gait parameters between EHC and patients with iNPH, with a clear improvement toward the normalization of the cadence and traveled arm distance postoperatively, and a clear improvement of the swing phase. Patients with iNPH with a good response to VP-shunt significantly differ from the non-responders with an ameliorated gait pattern

Gait pattern analysis in the home environment as a key factor for the reliable assessment of shunt responsiveness in patients with idiopathic normal pressure hydrocephalus

BACKGROUND: The identification of patients with gait disturbance associated with idiopathic normal pressure hydrocephalus (iNPH) is challenging. This is due to the multifactorial causes of gait disturbance in elderly people and the single moment examination of laboratory tests. OBJECTIVE: We aimed to assess whether the use of gait sensors in a patient's home environment could help establish a reliable diagnostic tool to identify patients with iNPH by differentiating them from elderly healthy controls (EHC). METHODS: Five wearable inertial measurement units were used in 11 patients with iNPH and 20 matched EHCs. Data were collected in the home environment for 72 h. Fifteen spatio-temporal gait parameters were analyzed. Patients were examined preoperatively and postoperatively. We performed an iNPH sub-group analysis to assess differences between responders vs. non-responders. We aimed to identify parameters that are able to predict a reliable response to VP-shunt placement. RESULTS: Nine gait parameters significantly differ between EHC and patients with iNPH preoperatively. Postoperatively, patients with iNPH showed an improvement in the swing phase (p = 0.042), and compared to the EHC group, there was no significant difference regarding the cadence and traveled arm distance. Patients with a good VP-shunt response (NPH recovery rate of ≥5) significantly differ from the non-responders regarding cycle time, cycle time deviation, number of steps, gait velocity, straight length, stance phase, and stance to swing ratio. A receiver operating characteristic analysis showed good sensitivity for a preoperative stride length of ≥0.44 m and gait velocity of ≥0.39 m/s. CONCLUSION: There was a significant difference in 60% of the analyzed gait parameters between EHC and patients with iNPH, with a clear improvement toward the normalization of the cadence and traveled arm distance postoperatively, and a clear improvement of the swing phase. Patients with iNPH with a good response to VP-shunt significantly differ from the non-responders with an ameliorated gait pattern

Self-regulation of the dopaminergic reward circuit in cocaine users with mental imagery and neurofeedback

BACKGROUND Enhanced drug-related reward sensitivity accompanied by impaired sensitivity to non-drug related rewards in the mesolimbic dopamine system are thought to underlie the broad motivational deficits and dysfunctional decision-making frequently observed in cocaine use disorder (CUD). Effective approaches to modify this imbalance and reinstate non-drug reward responsiveness are urgently needed. Here, we examined whether cocaine users (CU) can use mental imagery of non-drug rewards to self-regulate the ventral tegmental area and substantia nigra (VTA/SN). We expected that obsessive and compulsive thoughts about cocaine consumption would hamper the ability to self-regulate the VTA/SN activity and tested if real-time fMRI (rtfMRI) neurofeedback (NFB) can improve self-regulation of the VTA/SN. METHODS Twenty-two CU and 28 healthy controls (HC) were asked to voluntarily up-regulate VTA/SN activity with non-drug reward imagery alone, or combined with rtfMRI NFB. RESULTS On a group level, HC and CU were able to activate the dopaminergic midbrain and other reward regions with reward imagery. In CU, the individual ability to self-regulate the VTA/SN was reduced in those with more severe obsessive-compulsive drug use. NFB enhanced the effect of reward imagery but did not result in transfer effects at the end of the session. CONCLUSION CU can voluntary activate their reward system with non-drug reward imagery and improve this ability with rtfMRI NFB. Combining mental imagery and rtFMRI NFB has great potential for modifying the maladapted reward sensitivity and reinstating non-drug reward responsiveness. This motivates further work to examine the use of rtfMRI NFB in the treatment of CUD

Multimodal Monitoring Strategy Is Decisive in Elective Middle Cerebral Artery Aneurysm Clipping: A Case Report

BackgroundbThe intraoperative use of neurophysiological monitoring (IONM) and indocyanine green video angiography (ICGVA) for aneurysm clipping have evolved during the last years. Both modalities are useful and safe by allowing greater rates of complete aneurysm occlusion with less intraoperative complications and postoperative neurologic deficits. We report a case of attempted aneurysm clipping in which the combined use of ICGVA and IONM was crucial for intraoperative decision-making. Case Descriptionb A 62-year-old woman was operated for an incidental 6-mm aneurysm at the origin of the right fronto-opercular branch. During aneurysm clipping, IONM amplitudes dropped drastically, despite patency of the parent artery and perforators in ICGVA. Several attempts for clipping were made with recurring drops in IONM amplitudes, which forced us to leave the aneurysm untreated. The patient had a postoperative left-sided hemiparesis that improved on follow-up. Thereafter, the aneurysm was treated with stent-assisted coiling. Conclusions The combination of IONM and ICGVA during aneurysm surgery allows for a better assessment of vascular integrity and patient’s postoperative outcome than ICGVA alone. Simultaneous evaluation of vessel patency and integrity of the somatosensory and motor pathways illustrates the complementarity of testing different modalities for intraoperative decision-making and for maximizing safeness in aneurysm clipping

Safeness and utility of concomitant intraoperative monitoring with intraoperative magnetic resonance imaging in children - a pilot study

OBJECTIVE High-field intraoperative MR (ioMRI) has become increasingly available in neurosurgery centers. There is little experience with the combination of ioMRI with intraoperative neurophysiological neuromonitoring (IONM). We provide a first series of pediatric patients undergoing brain tumor surgery with 3T ioMRI and IONM. METHODS We conducted a pilot study were we included all consecutive children operated for brain tumors between October 2013 and April 2016 where concomitant ioMRI and somatosensory evoked potentials (SEP) and motor evoked potentials (MEP) were used. All cases were retrospectively analysed concerning neuromonitoring findings and related complications. RESULTS During a period of 30 months, 17 children (mean age 8.4 years; 3 females) were operated meeting the criteria. A total of 483 IONM needles were left in place during ioMRI. Of these needles, 119 were located on the scalp, 94 above the chest, and 270 below the chest. Two complications with skin burns (first degree) were observed. In all patients, neuromonitoring was still reliable after MRI. In one case, a threshold increase for MEP-stimulation (20 mA) was necessary after ioMRI; in two cases a reduction of 50% of the SEP amplitude at the end of the surgery was observed, when compared to the values obtained before ioMRI. CONCLUSIONS The combination of ioMRI and IONM can be safely performed in the pediatric population. IONM data acquisition after ioMRI was feasible and remained reliable

Effect of antisiphon devices on ventriculoperitoneal shunt drainage dynamics in growing children

OBJECTIVE Infants and small children face changing boundary conditions when treated with a ventriculoperitoneal shunt (VPS) for hydrocephalus. There are no systematic data describing shunt drainage behavior and changes over time in a growing child. Using a child-adapted patient simulator, the authors investigated the drainage behaviors of fixed differential pressure (DP) valves and adjustable valves with devices for preventing overdrainage in children of different ages. METHODS Three miniNAV DP valves with a 10–cm H2O medium-pressure setting (MN10) and three adjustable proGAV2.0 valves with a 25–cm H2O gravitational unit (GU) at low 5–cm H2O opening pressure (PG5) and medium 10–cm H2O opening pressure (PG10) settings were each investigated with a hardware-in-the-loop test bed. This test bed consisted of a posture motion mechanism and two pressure compartments that mimicked intracranial and abdominal pressures and was used to test the VPS under realistic in vitro conditions. Body orientation and length were physically set according to the child’s age. The software simulated the physiological situations of children aged 1, 5, and 10 years. All valves were tested according to these specifications, with 5 runs for 1 hour each in the horizontal, vertical, and horizontal positions. Intracranial pressure (ICP) and VPS flow were measured, and the respective cerebrospinal fluid volume changes and ICP set value were computed. RESULTS The drainage parameters increased with age in all valves in the vertical position, with that of MN10 being pronounced in the 1-year-old simulation. The GU values in PG5 and PG10 substantially reduced drainage compared with MN10. PG10 prevented drainage in the 1-year-old and 5-year-old setups, but there was some drainage at physiological ICP in the 10-year-old setup. In contrast, MN10 produced the largest decreases in ICP across all ages and positions, and overdrainage resulted in insufficient ICP recovery in the subsequent horizontal position. ICP levels were mostly constant with PG10 at all ages. CONCLUSIONS This study shows that unprotected DP valves may lead to overdrainage in infants, whereas low-pressure GU valves can prevent overdrainage through 5 years and medium-pressure GU valves admit physiological ICP through at least 10 years. Therefore, devices for preventing overdrainage should be included in the first implanted shunt, and opening pressure should be adjusted as the child grows.ISSN:1933-0707ISSN:1933-071

Human Resting-State Complexity of BOLD fMRI in Ultra-High-Field MRI at 7T: a primer

Synopsis Keywords: fMRI Analysis, fMRI (resting state), complexity Motivation: BOLD-fMRI intrinsic functional connectivity has limited capability to assess the temporal dynamics of complex brain networks. The insufficient signal-to-noise ratio of 3T MRI might prevent the detection of subtle alterations. Goal(s): Detecting resting-state complexity alterations in healthy subsamples using 7T MRI. Approach: Multiscale entropy was computed for ten scales from 0.1 to 1 Hz. A whole-brain ANCOVA was conducted to assess entropy differences of the scales between 30 healthy adults with spider phobia and 45 without. Results: Spider phobia showed decreased entropy in several fear-related brain regions in all scales except 1 Hz. Impact: 7T fMRI detected reduced high-frequency resting-state multiscale entropy related to spider phobia, indicating worse local processing of fear and memory-related brain regions. Introduction Intrinsic functional connectivity (iFC) derived from BOLD-fMRI data is still widely used to map the brain’s functional architecture at rest. Despite the substantial insight gained into diseased brain networks and corroborated markers for cognitive symptomatology, the method’s major shortcoming, one correlative metric over the entire scanning time, fails at characterizing the temporal dynamics of complex brain systems. Recently, multiscale entropy (MSE) analyses of resting-state BOLD fMRI signals have gained increased attention in basic and clinical neuroscience. MSE detects self-similarity of complex signals across multiple time scales in a random noise environment [1]. The MSE’s main advantage is that it can assess alterations and interactions of neuronal circuits on spatial and temporal scales. Hence, numerous studies have yielded novel insights into temporal dynamics of the brain’s functional reorganization [2-4]. Both iFC and MSE rely on a sufficient temporal and spatial signal-to-noise ratio (SNR) of the data. With advances in image processing algorithms, and especially with the availability of 7T MRI, images with increased SNR allow the detection of more subtle effects [5,6]. Hence, this study explored the MSE of a set of 7T BOLD-fMRI data that consisted of healthy participants, who were subdivided into a spider phobia (PH) and a control group (HC) sample. The rationale was to test whether MSE at 7T is sufficiently sensitive to detect MSE differences between these groups even though no spider images, the fear-triggering stimulus defining spider phobia, were shown during data acquisition. Nevertheless, assuming a hyperactive fear circuit in PH, we hypothesized decreased local processing complexity as measured with high-frequency MSE in brain regions involving the amygdala, hippocampus, parahippocampus, medial temporal lobe, fusiform gyrus, and anterior cingulate cortex [7]. Methods Study participant demographics and statistics are depicted in Figure 1. Resting-state fMRI data was obtained with a 32-channel head/neck coil in a Siemens Magnetom Terra 7T machine at the University Hospital Bern. A multiband echo-planar protocol with 360 measurements, 60 slices, TR/TE = 1000/25 ms, and iso-voxel size = 2 mm^3 was applied. Image preprocessing included motion-realignment, slice-time correction, detrending, denoising, normalization, and 3-mm-smoothing. MSE was computed using the LOFT Complexity Toolbox [8] with pattern matching threshold r = 0.2, pattern length = 2, scales = 1 – 10 (1 – 0.1 Hz) [9-11]. All images were masked with a mean grey matter mask of all subjects. Voxel-wise statistics were computed in SPM12 and comprised an ANCOVA with factors scale (1 – 10) and diagnosis (HC, PH), and age as a covariate. The significance threshold was pFWE < 0.05 and a cluster-size threshold of 5 voxels. Significant clusters were overlaid with the aal atlas [12-14] and segmented accordingly for a post-hoc ROI analysis, a non-parametric ANOVA investigating mean ROI entropy for each scale between the diagnosis groups. Results The voxel-wise interaction of the 2 × 10 ANCOVA revealed several significant clusters (F(9,729) = 5.49, p(FWE) = 0.05, cluster-size threshold = 5 voxels), which were subdivided into seven major regions of interest (ROIs): amygdala, caudate nucleus, fusiform gyrus, hippocampus, parahippocampus, putamen, and thalamus (Figure 2). To disentangle the two-way interaction involving these ROIs, the post-hoc ANOVA revealed the main effects of diagnosis (F(1) = 5.26, p = 0.02), ROI (F(3.8) = 20.0, p < 0.0001), and scale (F(1.5) = 114.8, p < 0.0001, see Figure 3). Merely the scale × ROI two-way interaction was significant (F(14) = 5.0, p < 0.0001). Note that the three-way interaction diagnosis × ROI × scale was not significant. Discussion This proof-of-concept study revealed reduced entropy in anxiety, memory, and emotion-regulation brain regions in PH compared to HC. Most brain regions with decreased MSE, such as the amygdala, hippocampus, parahippocampus, and fusiform gyrus, are hyperactive in PH [7]. The thalamus has been linked with autonomous arousal in PH [15], while the striatum, including putamen and caudate nucleus, was shown active during threat monitoring [16]. These MSE reductions were found in 9 of 10 frequencies (0.1 – 0.5 Hz). In the 1 Hz frequency, no group differences could be observed (Figure 3). With the scanning protocol used in this study, lower frequencies could not be assessed (i.e., < 0.1 Hz), which is a limitation and might explain the uniformity of the effects between most scales. Conclusions MSE analysis is a promising method that takes advantage of the higher temporal SNR of 7T fMRI, as demonstrated in this study. Using MSE as an add-on to iFC measures, a more refined picture of the dynamics of complex neuronal systems can be achieved. Acknowledgements This study was supported by the University Hospital for Psychiatry and Psychotherapy Bern, Switzerland. We thank the following contributors: Andrea Federspiel and Piotr Radojewski of the Translational Imaging Center (TIC), Swiss Institute for Translational and Entrepreneurial Medicine, Bern, Switzerland, for technical and clinical support at the MRI scanner site; Dilmini Wijesinghe of the Laboratory of FMRI Technology, USC Stevens Neuroimaging and Informatics Institute, University of Southern California, Keck School of Medicine, Los Angeles, California, USA, for providing valuable insight in fMRI complexity developments; Thomas Dierks of the Translational Research Center, University Hospital of Psychiatry and Psychotherapy, University of Bern, Switzerland, for conceptual advice. References 1. Costa M, Goldberger AL, Peng CK. Multiscale Entropy Analysis of Complex Physiologic Time Series. Phys Rev Lett. 2002;89(6):068102 2. Jann K, Boudreau J, Albrecht D, Cen SY, Cabeen RP, Ringman JM, Wang DJJ. FMRI Complexity Correlates with Tau-PET and Cognitive Decline in Late-Onset and Autosomal Dominant Alzheimer’s Disease. J Alz Dis. 2023;95(2):437-451 3. Grieder M, Wang DJJ, Dierks T, Wahlund LO, Jann K. Default Mode Network Complexity and Cognitive Decline in Mild Alzheimer’s Disease. Front Neurosci. 2018;12(770) 4. Xin X, Long S, Sun M, Gao X. The Application of Complexity Analysis in Brain Blood-Oxygen Signal. Brain Sci. 2021;11(11):1415 5. Dumoulin SO, Fracasso A, van der Zwaag W, Siero JCW, Petridou N. Ultra-high field MRI: Advancing systems neuroscience towards mesoscopic human brain function. NeuroImage. 2018;168:345-357 6. Pohmann R, Speck O, Scheffler K. Signal-to-noise ratio and MR tissue parameters in human brain imaging at 3, 7, and 9.4 tesla using current receive coil arrays. Magn Res Med. 2016;5(2):801-809 7. Soravia LM, Orosz A, Schwab S, Nakataki M, Wiest R, Federspiel A. CBT reduces CBF: cognitive-behavioral therapy reduces cerebral blood flow in fear-relevant brain regions in spider phobia. Brain Behav. 2016;6(9):e00510 8. Laboratory of Functional MRI Technology (LOFT), Department of Neurology, USC Developed by Jothi A, Sharma N, Adhikari S, Wang DJJ, Jann K 9. Li X, Zhu Z, Zhao W, Sun Y, Wen D, Xie Y, Liu X, Niu H, Han Y. Decreased resting-state brain signal complexity in patients with mild cognitive impairment and Alzheimer’s disease: a multi-scale entropy analysis. Biomed Opt Express. 2018;9(4):1916-1929 10. Smith RX, Yan L, Wang DJJ. Multiple time scale complexity analysis of resting state FMRI. Brain Imaging Behav. 2014;8:284–291 11. Sokunbi MO. Sample entropy reveals high discriminative power between young and elderly adults in short fMRI data sets. Front Neuroinform. 2014;8:69 12. Maldjian JA, Laurienti PJ, Kraft RA, Burdette JH. An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. NeuroImage. 2003;19(3):1233-9 13. Maldjian JA, Laurienti PJ, Burdette JH. Precentral gyrus discrepancy in electronic versions of the Talairach atlas. NeuroImage. 2004;21(1):450-5 14. Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N, Mazoyer B, Joliot M. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage. 2002;15(1):273-89 15. Del Casale A, Ferracuti S, Rapinesi C, Serata D, Piccirilli M, Savoja V, Kotzalidis GD, Manfredi G, Angeletti G, Tatarelli R, Girardi P. Functional neuroimaging in specific phobia. Psychiatr Res Neuroimaging. 2012;202(3):181-197 16. Mobbs D, Yu R, Rowe JB, Eich H, FeldmanHall O, Dalgleish T. Neural activity associated with monitoring the oscillating threat value of a tarantula. Proc Natl Acad Sci U S A. 2010;107(47):20582-2058

Effect of antisiphon devices on ventriculoperitoneal shunt drainage dynamics in growing children.

OBJECTIVE Infants and small children face changing boundary conditions when treated with a ventriculoperitoneal shunt (VPS) for hydrocephalus. There are no systematic data describing shunt drainage behavior and changes over time in a growing child. Using a child-adapted patient simulator, the authors investigated the drainage behaviors of fixed differential pressure (DP) valves and adjustable valves with devices for preventing overdrainage in children of different ages. METHODS Three miniNAV DP valves with a 10-cm H2O medium-pressure setting (MN10) and three adjustable proGAV2.0 valves with a 25-cm H2O gravitational unit (GU) at low 5-cm H2O opening pressure (PG5) and medium 10-cm H2O opening pressure (PG10) settings were each investigated with a hardware-in-the-loop test bed. This test bed consisted of a posture motion mechanism and two pressure compartments that mimicked intracranial and abdominal pressures and was used to test the VPS under realistic in vitro conditions. Body orientation and length were physically set according to the child's age. The software simulated the physiological situations of children aged 1, 5, and 10 years. All valves were tested according to these specifications, with 5 runs for 1 hour each in the horizontal, vertical, and horizontal positions. Intracranial pressure (ICP) and VPS flow were measured, and the respective cerebrospinal fluid volume changes and ICP set value were computed. RESULTS The drainage parameters increased with age in all valves in the vertical position, with that of MN10 being pronounced in the 1-year-old simulation. The GU values in PG5 and PG10 substantially reduced drainage compared with MN10. PG10 prevented drainage in the 1-year-old and 5-year-old setups, but there was some drainage at physiological ICP in the 10-year-old setup. In contrast, MN10 produced the largest decreases in ICP across all ages and positions, and overdrainage resulted in insufficient ICP recovery in the subsequent horizontal position. ICP levels were mostly constant with PG10 at all ages. CONCLUSIONS This study shows that unprotected DP valves may lead to overdrainage in infants, whereas low-pressure GU valves can prevent overdrainage through 5 years and medium-pressure GU valves admit physiological ICP through at least 10 years. Therefore, devices for preventing overdrainage should be included in the first implanted shunt, and opening pressure should be adjusted as the child grows

Ventriculomegaly in children: nocturnal ICP dynamics identify pressure-compensated but active paediatric hydrocephalus

INTRODUCTION Paediatric ventriculomegaly without obvious signs or symptoms of raised intracranial pressure (ICP) is often interpreted as resulting from either relative brain atrophy, arrested "benign" hydrocephalus, or "successful" endoscopic third ventriculostomy (ETV). We hypothesise that the typical ICP "signature" found in symptomatic hydrocephalus can be present in asymptomatic or oligosymptomatic children, indicating pressure-compensated, but active hydrocephalus. METHODS A total of 37 children fulfilling the mentioned criteria underwent computerised ICP overnight monitoring (ONM). Fifteen children had previous hydrocephalus treatment. ICP was analysed for nocturnal dynamics of ICP, ICP amplitudes (AMP), magnitude of slow waves (SLOW), and ICP/AMP correlation index RAP. Depending on the ONM results, children were either treated or observed. The ventricular width was determined at the time of ONM and at 1-year follow-up. RESULTS The recordings of 14 children (group A) were considered normal. In the 23 children with pathologic recordings (group B), all ICP values and dependent variables (AMP, SLOW) were significantly higher, except for RAP. In group B, 12 of 15 children had received a pre-treatment and 11 of 22 without previous treatment. All group B children received treatment for hydrocephalus and showed a significant reduction of frontal-occipital horn ratio at 1 year. During follow-up, a positive neurological development was seen in 74% of children of group A and 100% of group B. CONCLUSION Ventriculomegaly in the absence of signs and symptoms of raised ICP was associated in 62% of cases to pathological ICP dynamics. In 80% of pre-treated cases, ETV or shunt failure was found. Treating children with abnormal ICP dynamics resulted in an outcome at least as favourable as in the group with normal ICP dynamics. Thus, asymptomatic ventriculomegaly in children deserves further investigation and, if associated with abnormal ICP dynamics, should be treated in order to provide a normalised intracranial physiology as basis for best possible long-term outcome