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      Diagnostic Performance of Glymphatic System Evaluation Using Diffusion Tensor Imaging in Idiopathic Normal Pressure Hydrocephalus and Mimickers

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          Abstract

          Purpose

          To investigate the pathological change of the glymphatic system in idiopathic normal pressure hydrocephalus (iNPH) using diffusion tensor imaging (DTI) analysis.

          Materials and Methods

          24 right-handed patients were referred to our hydrocephalus clinic for assessment of ventriculomegaly and gait impairment. 12 of 24 were diagnosed as pseudo-iNPH (piNPH) based on assessment by a neurologist. Diffusivity maps in the direction of the x-axis (right-to-left) (Dx), y-axis (anterior-to-posterior) (Dy), and z-axis (inferior-to-superior) (Dz) were computed. The diffusion map was coregistered to International Consortium for Brain Mapping (ICBM) DTI-81 atlas. The analysis along the perivascular space (ALPS) index was defined as mean (Dxpro, Dypro)/mean (Dypro, Dzasc), where Dxpro and Dxasc are Dx values in the projection and association fiber areas, respectively. Evans index and callosal angle were also assessed on each case.

          Results

          ALPS indexes of the control, piNPH, and iNPH cases were 1.18 ± 0.08, 1.08 ± 0.03, and 0.94 ± 0.06, respectively, and there were significant differences among the groups (control vs. piNPH, P = 0.003; control vs. iNPH P < 0.001; piNPH vs. iNPH, P < 0.001). Area under curve (AUC) was 0.92, 1.00, and 1.00 on control vs. piNPH, control vs. iNPH, and piNPH vs. iNPH on ROC analysis. Between piNPH and NPH, ALPS index has higher diagnostic performance than Evans index and callosal angle (AUC = 1.00 vs. 0.84, P = 0.028; AUC = 1.00 vs. 0.74, P = 0.016).

          Conclusion

          Atlas-based ALPS index using the DTI method differentiated among iNPH, piNPH, and controls clearly.

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          Most cited references12

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          Evaluation of glymphatic system activity with the diffusion MR technique: diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer's disease cases.

          The activity of the glymphatic system is impaired in animal models of Alzheimer's disease (AD). We evaluated the activity of the human glymphatic system in cases of AD with a diffusion-based technique called diffusion tensor image analysis along the perivascular space (DTI-ALPS).
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            Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species

            Background The parenchyma of the brain does not contain lymphatics. Consequently, it has been assumed that arachnoid projections into the cranial venous system are responsible for cerebrospinal fluid (CSF) absorption. However, recent quantitative and qualitative evidence in sheep suggest that nasal lymphatics have the major role in CSF transport. Nonetheless, the applicability of this concept to other species, especially to humans has never been clarified. The purpose of this study was to compare the CSF and nasal lymph associations in human and non-human primates with those observed in other mammalian species. Methods Studies were performed in sheep, pigs, rabbits, rats, mice, monkeys and humans. Immediately after sacrifice (or up to 7 hours after death in humans), yellow Microfil was injected into the CSF compartment. The heads were cut in a sagittal plane. Results In the seven species examined, Microfil was observed primarily in the subarachnoid space around the olfactory bulbs and cribriform plate. The contrast agent followed the olfactory nerves and entered extensive lymphatic networks in the submucosa associated with the olfactory and respiratory epithelium. This is the first direct evidence of the association between the CSF and nasal lymph compartments in humans. Conclusions The fact that the pattern of Microfil distribution was similar in all species tested, suggested that CSF absorption into nasal lymphatics is a characteristic feature of all mammals including humans. It is tempting to speculate that some disorders of the CSF system (hydrocephalus and idiopathic intracranial hypertension for example) may relate either directly or indirectly to a lymphatic CSF absorption deficit.
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              Diagnostic intracranial pressure monitoring and surgical management in idiopathic normal pressure hydrocephalus: a 6-year review of 214 patients.

              To review our experience of managing idiopathic normal pressure hydrocephalus (iNPH) during the 6-year period from 2002 to 2007, when intracranial pressure (ICP) monitoring was part of the diagnostic workup. The review includes all iNPH patients undergoing diagnostic ICP monitoring during the years 2002 to 2007. Clinical grading was done prospectively using a normal pressure hydrocephalus (NPH) grading scale (scores from 3 to 15). The selection of patients for surgery was based on clinical symptoms, enlarged cerebral ventricles, and findings on ICP monitoring. The median follow-up time was 2 years (range, 0.3-6 years). Both static ICP and pulsatile ICP were analyzed. A total of 214 patients underwent the diagnostic workup, of whom 131 went on to surgery. Although 1 patient died shortly after treatment, 103 of the 130 patients (79%) improved clinically. This improvement lasted throughout the observation period. The static ICP observed during ICP monitoring was a poor predictor of the response to surgery. In contrast, among 109 of 130 patients with increased ICP pulsatility (ie, ICP wave amplitude >4 mm Hg on average and >5 mm Hg in >10% of recording time), 101 (93%) were responders (ie, increase in the NPH score of >2). Correspondingly, only 2 of 21 (10%) without increased ICP pulsatility were responders. Superficial wound infection was the only complication of ICP monitoring and occurred in 4 (2%) patients. Surgical results in iNPH were good with almost 80% of patients improving after treatment. The data indicate that improvement after surgery can be anticipated in 9 of 10 iNPH patients with abnormal ICP pulsatility, but in only 1 of 10 with normal ICP pulsatility. Diagnostic ICP monitoring had a low complication rate.
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                Author and article information

                Contributors
                Journal
                Curr Gerontol Geriatr Res
                Curr Gerontol Geriatr Res
                CGGR
                Current Gerontology and Geriatrics Research
                Hindawi
                1687-7063
                1687-7071
                2019
                20 June 2019
                : 2019
                : 5675014
                Affiliations
                1Chiba University, Department of Radiology, Chiba, Japan
                2UCLA Department of Radiological Sciences, Los Angeles, CA, USA
                3Toho University, Department of Neurosurgery, Ota, Tokyo, Japan
                4UCLA Department of Neurology, Los Angeles, CA, USA
                5UCLA Department of Neurosurgery, Los Angeles, CA, USA
                Author notes

                Academic Editor: Fulvio Lauretani

                Author information
                https://orcid.org/0000-0001-7362-9246
                Article
                10.1155/2019/5675014
                6609364
                f178df91-b751-47d4-8803-dd29221e782e
                Copyright © 2019 Hajime Yokota et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 December 2018
                : 22 May 2019
                : 4 June 2019
                Categories
                Research Article

                Geriatric medicine
                Geriatric medicine

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