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Continuous, noninvasive wireless monitoring of flow of cerebrospinal fluid through shunts in patients with hydrocephalus.

ABSTRACT: Hydrocephalus is a common disorder caused by the buildup of cerebrospinal fluid (CSF) in the brain. Treatment typically involves the surgical implantation of a pressure-regulated silicone tube assembly, known as a shunt. Unfortunately, shunts have extremely high failure rates and diagnosing shunt malfunction is challenging due to a combination of vague symptoms and a lack of a convenient means to monitor flow. Here, we introduce a wireless, wearable device that enables precise measurements of CSF flow, continuously or intermittently, in hospitals, laboratories or even in home settings. The technology exploits measurements of thermal transport through near-surface layers of skin to assess flow, with a soft, flexible, and skin-conformal device that can be constructed using commercially available components. Systematic benchtop studies and numerical simulations highlight all of the key considerations. Measurements on 7 patients establish high levels of functionality, with data that reveal time dependent changes in flow associated with positional and inertial effects on the body. Taken together, the results suggest a significant advance in monitoring capabilities for patients with shunted hydrocephalus, with potential for practical use across a range of settings and circumstances, and additional utility for research purposes in studies of CSF hydrodynamics.

SUBMITTER: Krishnan SR

PROVIDER: S-EPMC7060317 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Continuous, noninvasive wireless monitoring of flow of cerebrospinal fluid through shunts in patients with hydrocephalus.

Krishnan Siddharth R SR Arafa Hany M HM Kwon Kyeongha K Deng Yujun Y Su Chun-Ju CJ Reeder Jonathan T JT Freudman Juliet J Stankiewicz Izabela I Chen Hsuan-Ming HM Loza Robert R Mims Marcus M Mims Mitchell M Lee KunHyuck K Abecassis Zachary Z Banks Aaron A Ostojich Diana D Patel Manish M Wang Heling H Börekçi Kaan K Rosenow Joshua J Tate Matthew M Huang Yonggang Y Alden Tord T Potts Matthew B MB Ayer Amit B AB Rogers John A JA

NPJ digital medicine 20200306

Hydrocephalus is a common disorder caused by the buildup of cerebrospinal fluid (CSF) in the brain. Treatment typically involves the surgical implantation of a pressure-regulated silicone tube assembly, known as a shunt. Unfortunately, shunts have extremely high failure rates and diagnosing shunt malfunction is challenging due to a combination of vague symptoms and a lack of a convenient means to monitor flow. Here, we introduce a wireless, wearable device that enables precise measurements of CS ...[more]

PMID: 32195364

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Project description:IntroductionHydrocephalus is a complex neurological disorder with a pervasive impact on the central nervous system. Previous work has demonstrated derangements in the biochemical profile of cerebrospinal fluid (CSF) in hydrocephalus, particularly in infants and children, in whom neurodevelopment is progressing in parallel with concomitant neurological injury. The objective of this study was to examine the CSF of children with congenital hydrocephalus (CHC) to gain insight into the pathophysiology of hydrocephalus and identify candidate biomarkers of CHC with potential diagnostic and therapeutic value.MethodsCSF levels of amyloid precursor protein (APP) and derivative isoforms (sAPPα, sAPPβ, Aβ42), tau, phosphorylated tau (pTau), L1CAM, NCAM-1, aquaporin 4 (AQP4), and total protein (TP) were measured by ELISA in 20 children with CHC. Two comparative groups were included: age-matched controls and children with other neurological diseases. Demographic parameters, ventricular frontal-occipital horn ratio, associated brain malformations, genetic alterations, and surgical treatments were recorded. Logistic regression analysis and receiver operating characteristic curves were used to examine the association of each CSF protein with CHC.ResultsCSF levels of APP, sAPPα, sAPPβ, Aβ42, tau, pTau, L1CAM, and NCAM-1 but not AQP4 or TP were increased in untreated CHC. CSF TP and normalized L1CAM levels were associated with FOR in CHC subjects, while normalized CSF tau levels were associated with FOR in control subjects. Predictive ability for CHC was strongest for sAPPα, especially in subjects ≤12 months of age (p<0.0001 and AUC = 0.99), followed by normalized sAPPβ (p = 0.0001, AUC = 0.95), tau, APP, and L1CAM. Among subjects ≤12 months, a normalized CSF sAPPα cut-point of 0.41 provided the best prediction of CHC (odds ratio = 528, sensitivity = 0.94, specificity = 0.97); these infants were 32 times more likely to have CHC.ConclusionsCSF proteins such as sAPPα and related proteins hold promise as biomarkers of CHC in infants and young children, and provide insight into the pathophysiology of CHC during this critical period in neurodevelopment.

Project description:Objective The combination of cranioplasty and ventriculoperitoneal shunt is a therapeutic strategy for patients with hydrocephalus after decompressive craniectomy (DC). However, the efficacies of simultaneous vs. staged surgery in reducing postoperative complications have not been conclusively determined. This was a meta-analysis of relevant studies to assess whether simultaneous surgery significantly reduces postoperative complication risks, compared to staged surgery. Methods We systematically searched PubMed, Embase, Cochrane, Web of science databases for studies (published by 11 May 2022) comparing patients undergoing concurrent and staged cranioplasty and ventriculoperitoneal shunt. Our main endpoints were; overall postoperative complications, postoperative bleeding, postoperative infection and reoperation. We assessed the pooled data using a random effects model to compare complication rates using odds ratios (ORs) and 95% confidence intervals (CIs). Results Of the 494 identified studies, 12 were included in our analysis (N = 651 participants). Compared to staged surgery, concurrent surgery increased the relative risk for overall complications (pooled OR: 2.00; 95% CI: 1.10–3.67), however, it did not increase the relative risks for postoperative bleeding, postoperative infection or reoperation. Subgroup analysis revealed that in the Asian population, concurrent surgery increased the relative risks for overall complications (staged vs. concurrent group: OR: 2.41, 95% CI: 1.51–3.83, I2 = 0.0%) and postoperative infections (staged vs. concurrent group: OR: 2.35, 95% CI: 1.06–5.21, I2 = 31.8%). Conclusion Compared to staged surgery, concurrent surgery increases the overall complication rates. However, differences between the two therapeutic approaches in terms of postoperative bleeding, postoperative infection, or reoperation are insignificant. Simultaneous surgery was associated with increased overall post-operative complications and post-operative infection rates in the Asian population.

Project description:Background and Purpose- Preterm neonates with intraventricular hemorrhage (IVH) are at risk for posthemorrhagic hydrocephalus and poor neurological outcomes. Iron has been implicated in ventriculomegaly, hippocampal injury, and poor outcomes following IVH. We hypothesized that levels of cerebrospinal fluid blood breakdown products and endogenous iron clearance proteins in neonates with IVH differ from those of neonates with IVH who subsequently develop posthemorrhagic hydrocephalus. Methods- Premature neonates with an estimated gestational age at birth <30 weeks who underwent lumbar puncture for clinical evaluation an average of 2 weeks after birth were evaluated. Groups consisted of controls (n=16), low-grade IVH (grades I-II; n=4), high-grade IVH (grades III-IV; n=6), and posthemorrhagic hydrocephalus (n=9). Control subjects were preterm neonates born at <30 weeks' gestation without brain abnormality or hemorrhage on cranial ultrasound, who underwent lumbar puncture for clinical purposes. Cerebrospinal fluid hemoglobin, total bilirubin, total iron, ferritin, ceruloplasmin, transferrin, haptoglobin, and hemopexin were quantified. Results- Cerebrospinal fluid hemoglobin levels were increased in posthemorrhagic hydrocephalus compared with high-grade IVH (9.45 versus 6.06 µg/mL, P<0.05) and cerebrospinal fluid ferritin levels were increased in posthemorrhagic hydrocephalus compared with controls (511.33 versus 67.08, P<0.01). No significant group differences existed for the other cerebrospinal fluid blood breakdown and iron-handling proteins tested. We observed positive correlations between ventricular enlargement (frontal occipital horn ratio) and ferritin (Pearson r=0.67), hemoglobin (Pearson r=0.68), and total bilirubin (Pearson r=0.69). Conclusions- Neonates with posthemorrhagic hydrocephalus had significantly higher levels of hemoglobin than those with high-grade IVH. Levels of blood breakdown products, hemoglobin, ferritin, and bilirubin correlated with ventricular size. There was no elevation of several iron-scavenging proteins in cerebrospinal fluid in neonates with posthemorrhagic hydrocpehalus, indicative of posthemorrhagic hydrocephalus as a disease state occurring when endogenous iron clearance mechanisms are overwhelmed.

Dataset Information

Continuous, noninvasive wireless monitoring of flow of cerebrospinal fluid through shunts in patients with hydrocephalus.

Publications

Continuous, noninvasive wireless monitoring of flow of cerebrospinal fluid through shunts in patients with hydrocephalus.

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