scholarly journals Elevated CSF inflammatory markers in patients with idiopathic normal pressure hydrocephalus do not promote NKCC1 hyperactivity in rat choroid plexus

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Sara Diana Lolansen ◽  
Nina Rostgaard ◽  
Søren Norge Andreassen ◽  
Anja Hviid Simonsen ◽  
Marianne Juhler ◽  
...  
Keyword(s):  
Choroid Plexus ◽  
Clinical Improvement ◽  
Normal Pressure Hydrocephalus ◽  
Inflammatory Markers ◽  
Ex Vivo ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Control Subjects ◽  
Csf Shunting ◽  
Elderly Control

Abstract Background Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible neurological condition of unresolved etiology characterized by a clinical triad of symptoms; gait disturbances, urinary incontinence, and cognitive deterioration. In the present study, we aimed to elucidate the molecular coupling between inflammatory markers and development of iNPH and determine whether inflammation-induced hyperactivity of the choroidal Na+/K+/2Cl− cotransporter (NKCC1) that is involved in cerebrospinal fluid (CSF) secretion could contribute to the iNPH pathogenesis. Methods Lumbar CSF samples from 20 iNPH patients (10 with clinical improvement upon CSF shunting, 10 without clinical improvement) and 20 elderly control subjects were analyzed with the novel proximity extension assay technique for presence of 92 different inflammatory markers. RNA-sequencing was employed to delineate choroidal abundance of the receptors for the inflammatory markers found elevated in the CSF from iNPH patients. The ability of the elevated inflammatory markers to modulate choroidal NKCC1 activity was determined by addition of combinations of rat version of these in ex vivo experiments on rat choroid plexus. Results 11 inflammatory markers were significantly elevated in the CSF from iNPH patients compared to elderly control subjects: CCL28, CCL23, CCL3, OPG, CXCL1, IL-18, IL-8, OSM, 4E-BP1, CXCL6, and Flt3L. One inflammatory marker, CDCP1, was significantly decreased in iNPH patients compared to control subjects. None of the inflammatory markers differed significantly when comparing iNPH patients with and without clinical improvement upon CSF shunting. All receptors for the elevated inflammatory markers were expressed in the rat and human choroid plexus, except CCR4 and CXCR1, which were absent from the rat choroid plexus. None of the elevated inflammatory markers found in the CSF from iNPH patients modulated the choroidal NKCC1 activity in ex vivo experiments on rat choroid plexus. Conclusion The CSF from iNPH patients contains elevated levels of a subset of inflammatory markers. Although the corresponding inflammatory receptors are, in general, expressed in the choroid plexus of rats and humans, their activation did not modulate the NKCC1-mediated fraction of choroidal CSF secretion ex vivo. The molecular mechanisms underlying ventriculomegaly in iNPH, and the possible connection to inflammation, therefore remains to be elucidated.

scholarly journals Decreases in Ventricular Volume Correlate with Decreases in Ventricular Pressure in Idiopathic Normal Pressure Hydrocephalus Patients Who Experienced Clinical Improvement after Implantation with Adjustable Valve Shunts

Neurosurgery ◽  
2004 ◽  
Vol 55 (3) ◽  
pp. 582-593 ◽  
Author(s):  
Kathleen A. McConnell ◽  
Kelly H. Zou ◽  
Alexandra V. Chabrerie ◽  
Nancy Olsen Bailey ◽  
Peter McL. Black
Keyword(s):  
Correlation Coefficient ◽  
Clinical Improvement ◽  
Normal Pressure Hydrocephalus ◽  
Normal Pressure ◽  
Ventricular Volume ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Adjustable Valve ◽  
Programmable Valve ◽  
Valve Pressure ◽  
Over Time

Abstract OBJECTIVE: This retrospective study examined whether changes in ventricular volume correspond with changes in adjustable valve pressure settings in a cohort of patients who received shunts to treat idiopathic normal pressure hydrocephalus. We also examined whether these pressure–volume curves and other patient variables would co-occur with a positive clinical response to shunting. METHODS: We selected 51 patients diagnosed with idiopathic normal pressure hydrocephalus who had undergone implantation of a Codman Hakim programmable valve (Medos S.A., Le Locle, Switzerland). Clinical data were gathered from the patients' records and clinical notes by an investigator blinded to patients' ventricular volumes. Ventricular volume was measured using 3D Slicer, an image analysis and interactive visualization software package developed and maintained at the Surgical Planning Laboratory at Brigham and Women's Hospital. RESULTS: Eighty-six percent of patients with gait disturbance at presentation showed improvement of this symptom, 70% experienced improvement in incontinence, and 69% experienced improvement in dementia. For the group showing 100% clinical improvement, the correlation coefficient of average changes in valve pressure over time (ΔP/ΔT) and average changes in ventricular volume over time (ΔV/ΔT) were high at 0.843 (P < 0.05). For the group experiencing no or only partial improvement, the correlation coefficient was 0.257 (P = 0.32), indicating no correlation between average ΔV/ΔT and average ΔP/ΔT for each patient. CONCLUSION: This was a carefully analyzed modeling study of idiopathic normal pressure hydrocephalus treatment made possible only by adjustable valve technology. With careful volumetric analysis, we found that changes in ventricular volume correlated with adjustments in valve pressure settings for those patients who improved clinically after shunting. This suggests that positive clinical responders retained parenchymal elasticity, emphasizing the importance of dynamic changes in this cohort.

scholarly journals Postshunt Cognitive and Functional Improvement in Idiopathic Normal Pressure Hydrocephalus

Neurosurgery ◽  
2011 ◽  
Vol 68 (2) ◽  
pp. 416-419 ◽  
Author(s):  
Heather Katzen ◽  
Lisa D. Ravdin ◽  
Stephanie Assuras ◽  
Roberto Heros ◽  
Michael Kaplitt ◽  
...  
Keyword(s):  
Normal Pressure Hydrocephalus ◽  
Repeated Measures ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Practice Effects ◽  
Control Group ◽  
Significant Group ◽  
Shunt Placement ◽  
Cognitive Improvement ◽  
Control Subjects

Abstract BACKGROUND: Improvement in gait after shunt placement has been well documented in idiopathic normal pressure hydrocephalus (iNPH); however, controversy remains regarding the extent and pattern of postsurgical cognitive changes. Conflicting findings may be explained by variability in both test selection and follow-up intervals across studies. Furthermore, most investigations lack a control group, making it difficult to disentangle practice effects from a true treatment effect. OBJECTIVE: To examine postshunt changes in a sample of well-characterized iNPH participants compared with a group of age- and education-matched healthy control subjects. METHODS: We identified 12 participants with iNPH undergoing shunt placement and 9 control participants. All participants were evaluated with comprehensive neuropsychological testing and standardized gait assessment at baseline and were followed up for 6 months. RESULTS: Repeated-measures analysis of variance revealed a significant group- (iNPH and control) by-time (baseline and 6 months) interaction for Trailmaking Test B: (P < .003) and Symbol Digit Modalities (P < .02), with greater improvement in iNPH participants relative to control subjects. In addition, the iNPH group showed greater improvement in gait (P < .001) and caregivers reported improved activities of daily living (P < .01) and reduced caregiver distress (P < .01). CONCLUSION: This study demonstrates improvements in mental tracking speed and sustained attention 6 months after shunt placement in iNPH. The present investigation is the first study to use a controlled design to show that cognitive improvement in iNPH is independent of practice effects. Furthermore, these findings indicate functional and quality-of-life improvements for both the shunt responder and their caregiver.

scholarly journals Delayed clearance of cerebrospinal fluid tracer from choroid plexus in idiopathic normal pressure hydrocephalus

2019 ◽  
Vol 40 (9) ◽  
pp. 1849-1858 ◽  
Author(s):  
Per Kristian Eide ◽  
Lars Magnus Valnes ◽  
Are Hugo Pripp ◽  
Kent-Andre Mardal ◽  
Geir Ringstad
Keyword(s):  
Magnetic Resonance Imaging ◽  
Cerebrospinal Fluid ◽  
Magnetic Resonance ◽  
Choroid Plexus ◽  
Normal Pressure Hydrocephalus ◽  
Amyloid Β ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Resonance Imaging ◽  
Lateral Ventricles

Impaired clearance of amyloid-β from choroid plexus is one proposed mechanism behind amyloid deposition in Alzheimer's disease. The present study examined whether clearance from choroid plexus of a cerebrospinal fluid tracer, serving as a surrogate marker of a metabolic waste product, is altered in idiopathic normal pressure hydrocephalus (iNPH), one sub-type of dementia. In a prospective observational study of close to healthy individuals (reference cohort; REF) and individuals with iNPH, we performed standardized T1-weighted magnetic resonance imaging scans before and through 24 h after intrathecal administration of a cerebrospinal fluid tracer (the magnetic resonance imaging contrast agent gadobutrol). Changes in normalized T1 signal within the choroid plexus and cerebrospinal fluid of lateral ventricles were quantified using FreeSurfer. The normalized T1 signal increased to maximum within choroid plexus and cerebrospinal fluid of lateral ventricles 6–9 h after intrathecal gadobutrol in both the REF and iNPH cohorts (enrichment phase). Peak difference in normalized T1 signals between REF and iNPH individuals occurred after 24 h (clearance phase). The results gave evidence for gadobutrol resorption from cerebrospinal fluid by choroid plexus, but with delay in iNPH patients. Whether choroid plexus has a role in iNPH pathogenesis in terms of delayed clearance of amyloid-β remains to be shown.

scholarly journals Cerebrospinal Fluid Amyloid-β Oligomer Levels in Patients with Idiopathic Normal Pressure Hydrocephalus

2021 ◽  
pp. 1-12
Author(s):  
Kaito Kawamura ◽  
Masakazu Miyajima ◽  
Madoka Nakajima ◽  
Mitsuyasu Kanai ◽  
Yumiko Motoi ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Normal Pressure Hydrocephalus ◽  
Characteristic Curve ◽  
Amyloid Β ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Cognitive Outcome ◽  
Neurological Improvement ◽  
Csf Shunting ◽  
Before And After

Background: The amyloid-β oligomers, consisting of 10–20 monomers (AβO10–20), have strong neurotoxicity and are associated with cognitive impairment in Alzheimer’s disease (AD). However, their role in patients with idiopathic normal pressure hydrocephalus (iNPH) is poorly understood. Objective: We hypothesized that cerebrospinal fluid (CSF) AβO10–20 accumulates in patients with iNPH, and its clearance after CSF shunting contributes to neurological improvement. We measured CSF AβO10–20 levels before and after CSF shunting in iNPH patients evaluating their diagnostic and prognostic role. Methods: We evaluated two iNPH cohorts: “evaluation” (cohort-1) with 32 patients and “validation” (cohort-2) with 13 patients. Comparison cohorts included: 27 neurologically healthy controls (HCs), and 16 AD, 15 Parkinson’s disease (PD), and 14 progressive supranuclear palsy (PSP) patients. We assessed for all cohorts CSF AβO10–20 levels and their comprehensive clinical data. iNPH cohort-1 pre-shunting data were compared with those of comparison cohorts, using cohort-2 for validation. Next, we compared cohort-1’s clinical and CSF data: 1) before and after CSF shunting, and 2) increased versus decreased AβO10–20 levels at baseline, 1 and 3 years after shunting. Results: Cohort-1 had higher CSF AβO10–20 levels than the HCs, PD, and PSP cohorts. This result was validated with data from cohort-2. CSF AβO10–20 levels differentiated cohort-1 from the PD and PSP groups, with an area under receiver operating characteristic curve of 0.94. AβO10–20 levels in cohort-1 decreased after CSF shunting. Patients with AβO10–20 decrease showed better cognitive outcome than those without. Conclusion: AβO10–20 accumulates in patients with iNPH and is eliminated by CSF shunting. AβO10–20 can be an applicable diagnostic and prognostic biomarker.

ENDOSCOPIC THIRD VENTRICULOSTOMY IN IDIOPATHIC NORMAL PRESSURE HYDROCEPHALUS

Neurosurgery ◽  
2008 ◽  
Vol 63 (1) ◽  
pp. 62-69 ◽  
Author(s):  
ichelangelo Gangemi ◽  
Francesco Maiuri ◽  
Michele Naddeo ◽  
Umberto Godano ◽  
Carmelo Mascari ◽  
...  
Keyword(s):  
Clinical Improvement ◽  
Normal Pressure Hydrocephalus ◽  
Endoscopic Third Ventriculostomy ◽  
Clinical History ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Third Ventriculostomy ◽  
Patient Age ◽  
Clinical Onset ◽  
Patient Âgé

ABSTRACT OBJECTIVES The aim of the report is to define the indications and results of endoscopic third ventriculostomy (ETV) in idiopathic normal pressure hydrocephalus and to discuss the physiopathological mechanism of this procedure. METHODS The cases of 110 patients with idiopathic normal pressure hydrocephalus who underwent ETV in four Italian neurosurgical centers were retrospectively reviewed. The postoperative outcome was correlated with patient age, length of clinical history, preoperative clinical score, symptoms of clinical onset, type of hydrocephalus, and intraoperative findings. RESULTS The follow-up period ranged from 2 to 12 years (average, 6.5 yr). The outcome evaluation was made 2 years after the procedure. Postoperative clinical improvement occurred in 76 (69.1%) of 110 patients. There was no correlation between success rate and patient age or type of ventricular enlargement (normal or enlarged fourth ventricle). Conversely, the rate of neurological improvement was higher in patients with shorter clinical history, better preoperative neurological score, and clinical onset with gait disturbances. Moreover, the intraoperative finding of the sudden reappearance of normal cerebral pulsations and significant downward and upward movements of the third ventricular floor after ETV was also correlated with a good outcome. CONCLUSION ETV results in a relatively high rate of clinical improvement and a low complication rate in patients with idiopathic normal pressure hydrocephalus. Therefore, it may be easily performed with the same approach used for intracranial pressure monitoring with low morbidity. However, our data must be confirmed by additional studies.

scholarly journals P.125 Is idiopathic normal pressure hydrocephalus familial—what do we know thus far? Case report and critique of the literature

2018 ◽  
Vol 45 (s2) ◽  
pp. S49-S49
Author(s):  
H Li ◽  
K Meguro
Keyword(s):  
Normal Pressure Hydrocephalus ◽  
Case Reports ◽  
Retrospective Chart Review ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Symptom Improvement ◽  
Csf Shunting ◽  
Family Case ◽  
Family Case Study

Background: One aspect of idiopathic normal pressure hydrocephalus (iNPH) that has garnered interest is whether it can be familial. Thus far, the literature consists of several case reports, and two larger pedigree cohorts. Our objective is to highlight key deficiencies in such studies so far, illustrating them through a family case study of our own, and to propose a set of criteria that studies on familial iNPH should incorporate. Methods: Our case study is a retrospective chart review of three siblings, two male and one female, who were diagnosed with iNPH after the age of 60, and whose symptoms improved with cerebrospinal fluid (CSF) shunting. An interview with them revealed that their mother also exhibited symptoms of iNPH, but was never treated with a shunt. Results: Our family case is reflective of several deficiencies of familial iNPH research as a whole—unconfirmed diagnosis, especially confirmation with shunt responsiveness, and lack of measures of symptom improvement. Conclusions: Research on familial iNPH should focus on patients whose diagnosis is confirmed by shunt responsiveness, and should involve a system to objectively measure signs of NPH. Studies should also compare the prevalence of iNPH among first degree relatives of NPH patients to that in the general population.

scholarly journals A double-blind randomized trial on the clinical effect of different shunt valve settings in idiopathic normal pressure hydrocephalus

2016 ◽  
Vol 124 (2) ◽  
pp. 359-367 ◽  
Author(s):  
Dan Farahmand ◽  
Terje Sæhle ◽  
Per Kristian Eide ◽  
Magnus Tisell ◽  
Per Hellström ◽  
...  
Keyword(s):  
Clinical Improvement ◽  
Normal Pressure Hydrocephalus ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Double Blind ◽  
Shunt Valve ◽  
Shunt Insertion ◽  
Significant Clinical Improvement ◽  
Medium Level ◽  
Double Blinded

OBJECT The study aim was to examine the effect of gradually reducing the opening pressure on symptoms and signs in the shunt treatment of idiopathic normal pressure hydrocephalus (iNPH). METHODS In this prospective double-blinded, randomized, controlled, double-center study on patients with iNPH, a ventriculoperitoneal shunt with an adjustable Codman Medos Valve was implanted in 68 patients randomized into 2 groups. In 1 group (the 20–4 group) the valve setting was initially set to 20 cm H2O and gradually reduced to 4 cm H2O over the course of the 6-month study period. In the other group (the 12 group), the valve was kept at a medium level of 12 cm H2O during the whole study period. All patients were clinically evaluated using 4 tests preoperatively as well as postoperatively at 1, 2, 3, 4, and 6 months. The test scores between the 2 groups (20–4 and 12) were compared for each clinical evaluation. RESULTS Fifty-five patients (81%) were able to complete the study. There were no significant differences between the 2 groups (20–4 and 12) preoperatively or at any time postoperatively. Both groups exhibited significant clinical improvement after shunt insertion at all valve settings compared with the preoperative score, with the greatest improvement observed at the first postoperative evaluation. The clinical improvement was significant within the first 3 months, and thereafter no significant improvement was seen in either group. CONCLUSIONS Gradual reduction of the valve setting from 20 to 4 cm H2O did not improve outcome compared with a fixed valve setting of 12 cm H2O. Improvement after shunt surgery in iNPH patients was evident within 3 months, irrespective of valve setting.

scholarly journals Cerebrospinal fluid levels of amyloid-beta oligomers in patients with idiopathic normal pressure hydrocephalus are elevated before shunt surgery but decrease afterward

2020 ◽  
Author(s):  
Kaito Kawamura ◽  
Masakazu Miyajima ◽  
Madoka Nakajima ◽  
Mitsuyasu Kanai ◽  
Yumiko Motoi ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Amyloid Beta ◽  
Normal Pressure Hydrocephalus ◽  
Characteristic Curve ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Csf Shunting ◽  
Before And After ◽  
Neurologically Normal ◽  
Aβ Oligomer

Abstract Background The amyloid-beta (Aβ) oligomer has strong neurotoxicity and is associated with cognitive impairment in Alzheimer’s disease (AD). However, its role in patients with idiopathic normal pressure hydrocephalus (iNPH) is poorly understood. We hypothesised that cerebrospinal fluid (CSF) stagnation leads to Aβ oligomer accumulation in patients with iNPH. We measured CSF Aβ oligomer levels before and after CSF shunting in patients with iNPH. Methods We evaluated two iNPH cohorts: an analysis cohort (cohort-1) with 52 patients and a validation cohort (cohort-2) with 13 patients. For comparison cohorts, we recruited 27 neurologically normal controls (NCs), 16 patients with AD, 15 patients with Parkinson’s disease (PD), and 14 patients with progressive supranuclear palsy (PSP). We measured CSF Aβ oligomer levels and assessed participants’ neurological statuses. We then compared the iNPH cohorts’ pre-shunting measurements with the comparison groups’ measurements and compared cohort-1’s measurements recorded before and after CSF shunting. Results iNPH cohort-1 had higher CSF Aβ oligomer levels than the NC, PD, and PSP cohorts. This result was validated with data from iNPH cohort-2. CSF Aβ oligomer levels differentiated iNPH cohort-1 from the PD and PSP groups, with an area under receiver operating characteristic curve of 0.94. Aβ oligomer levels in iNPH cohort-1 decreased after CSF shunting. However, there was no correlation between Aβ oligomer levels and cognitive functions in iNPH cohort-1. Conclusion The Aβ oligomer accumulates in patients with iNPH patients but can be eliminated with CSF shunting, suggesting that CSF stagnation causes Aβ oligomer accumulation in iNPH.

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