Background and purpose
Protein tyrosine phosphatase receptor type Q (PTPRQ) was extracted from the cerebrospinal fluid (CSF) of patients with probable idiopathic normal‐pressure hydrocephalus (iNPH) ...by proteome analysis. We aimed to assess the feasibility of using CSF PTPRQ concentrations for the additional diagnostic criterion of iNPH in Japanese and Finnish populations.
Methods
We compared PTPRQ concentrations among patients with probable iNPH and neurologically healthy individuals (normal control NC group), patients with normal‐pressure hydrocephalus (NPH) of acquired and congenital/developmental aetiologies, patients with Alzheimer’s disease and patients with Parkinson’s disease in a Japanese analysis cohort. A corresponding iNPH group and NC group in a Finnish cohort was used for validation. Patients in the Finnish cohort who underwent biopsy were classified into two groups based on amyloid and/or tau deposition. We measured PTPRQ expression levels in autopsied brain specimens of iNPH patients and the NC group.
Results
Cerebrospinal fluid PTPRQ concentrations in the patients with NPH of idiopathic, acquired and congenital/developmental aetiologies were significantly higher than those in the NC group and those with Parkinson’s disease, but iNPH showed no significant differences when compared with those in the Alzheimer’s disease group. For the patients with iNPH, the area under the receiver‐operating characteristic curve was 0.860 in the Japanese iNPH and 0.849 in the Finnish iNPH cohorts. Immunostaining and in situ hybridization revealed PTPRQ expression in the ependymal cells and choroid plexus. It is highly possible that the elevated PTPRQ levels in the CSF are related to ependymal dysfunction from ventricular expansion.
Conclusions
Cerebrospinal fluid PTPRQ levels indicated the validity of this assay for auxiliary diagnosis of adult chronic hydrocephalus.
Protein tyrosine phosphatase receptor type Q (PTPRQ) extracted from CSF of patients with probable idiopathic normal pressure hydrocephalus (iNPH) by proteome analysis was evaluated as potential biomarker for this condition. Its level from two cohorts ‐ Japanese and Finnish was compared with normal controls and non‐iNPH patients. The levels were significantly lower than non‐iNPH patients, but higher than normal controls. It is highly possible that the elevated PTPRQ levels in CSF are related to ependymal dysfunction from ventricular expansion. CSF PTPRQ levels indicated the validity of this assay for auxiliary diagnosis of adult chronic hydrocephalus.
Studies have suggested that arachnoid villi or granulations found in the walls of the cranial dural sinuses, olfactory mucosa, and cranial nerve sheaths function as outlets for intracranial CSF. ...However, their role as CSF outlets has not yet been verified. Here we show that arachnoid protrusions and contiguous diploic veins provide an alternative drainage route for intracranial CSF.
Four hundred patients with intact skull, dura mater, and dural sinuses underwent MR imaging to explore arachnoids protruding into the skull and diploic veins. Patients with symptoms of increased intracranial pressure or intracranial hypotension were excluded. For 15 patients undergoing craniotomy, both peripheral and diploic venous blood was collected. Albumin and the CSF-specific biomarkers were measured by enzyme-linked immunosorbent assay.
With MR imaging, arachnoid protrusions into the skull and contiguous diploic veins were consistently identified throughout the cranium with their characteristic appearance depending on the cranial region. In addition, elevated amounts of prostaglandin D synthase and cystatin C were confirmed in diploic veins compared with peripheral venous blood.
Diploic veins are distributed ubiquitously throughout the cranium. A portion of the intracranial CSF may be drained through arachnoid protrusions and contiguous diploic veins.
Background Cognitive impairment is difficult to improve after shunt operation in patients with idiopathic normal pressure hydrocephalus (iNPH). This study aims to identify cerebrospinal fluid (CSF) ...biomarkers predictive of improvement in cognitive function. Methods This study was conducted between January 2008 and December 2010 on consecutive, unselected admissions to our program for the treatment of patients with clinically suspected iNPH. Lumbar CSF concentrations of total tau (Tau), tau phosphorylated at threonine 181 (p-tau), soluble amyloid precursor protein (sAPP), sAPPalpha, sAPPbeta, and beta-amyloid1-42 (Abeta42) were analyzed by ELISA. Results Concentrations of p-tau, sAPP, sAPPalpha, and sAPPbeta were strong diagnostic biomarkers for distinguishing between iNPH and Alzheimer's disease (AD). sAPPalpha exhibited the highest accuracy in differentiating iNPH from patients with AD and normal controls, with an area under the curve value of 0.994. We examined the prognostic value of p-tau and sAPPalpha for cognition function after surgery. With a cutoff value of 198 ng/ml or less for sAPPalpha, sensitivity and specificity are 66.7% and 82.9%, respectively, whilst the Mini-Mental State Examination score at 6 months after surgery is expected to be 25 or more. Conclusion Our results show that sAPPalpha is a suitable biomarker for the diagnosis and prognosis of iNPH. PUBLICATION ABSTRACT
Background
Cognitive impairment is difficult to improve after shunt operation in patients with idiopathic normal pressure hydrocephalus (iNPH). This study aims to identify cerebrospinal fluid (CSF) ...biomarkers predictive of improvement in cognitive function.
Methods
This study was conducted between January 2008 and December 2010 on consecutive, unselected admissions to our program for the treatment of patients with clinically suspected iNPH. Lumbar CSF concentrations of total tau (Tau), tau phosphorylated at threonine 181 (p‐tau), soluble amyloid precursor protein (sAPP), sAPPα, sAPPβ, and β‐amyloid1‐42 (Aβ42) were analyzed by ELISA.
Results
Concentrations of p‐tau, sAPP, sAPPα, and sAPPβ were strong diagnostic biomarkers for distinguishing between iNPH and Alzheimer's disease (AD). sAPPα exhibited the highest accuracy in differentiating iNPH from patients with AD and normal controls, with an area under the curve value of 0.994. We examined the prognostic value of p‐tau and sAPPα for cognition function after surgery. With a cutoff value of 198 ng/ml or less for sAPPα, sensitivity and specificity are 66.7% and 82.9%, respectively, whilst the Mini‐Mental State Examination score at 6 months after surgery is expected to be 25 or more.
Conclusion
Our results show that sAPPα is a suitable biomarker for the diagnosis and prognosis of iNPH.
Objectives
The cerebrospinal fluid tap test for idiopathic normal pressure hydrocephalus (iNPH) is one of the good predictors of the shunt treatment, although this test has a low sensitivity. We ...aimed to identify key parameters that could be used to improve this sensitivity.
Materials & methods
During 2010–2011, we recruited and then followed 93 patients with possible iNPH for 12 months after shunt. Among them, 82 patients were finally enrolled in this study. The modified Rankin Scale, iNPH grading scale, and several quantitative measurements were evaluated at entry, after the tap test, before and after shunt. Area under the receiver‐operating characteristic curves (AUCs), sensitivities, and specificities of the tap test for predicting shunt effectiveness were calculated for each measurement. They were additionally assessed after stratification by disease duration since the initial presentation of iNPH symptoms.
Results
The gait disturbance on the iNPH grading scale had the highest accurate scale at the tap test for predicting effectiveness 12 months after shunt: AUC 0.74, sensitivity 56.5%, specificity 91.7%. This AUC increased to 0.76, 0.91 and 0.94 in the subgroup of disease duration <24, <12, and <6 months, respectively. The sensitivity and specificity of the gait disturbance on the iNPH grading scale in the subgroup of <12 months' duration were 92.3% and 90.0%.
Conclusions
The shorter period of clinical symptoms, for example, <12 months, made the tap test sufficiently accurate examination for predicting improvement 12 months after shunt surgery. The findings imply that the tap test should be applied to patients being considered for shunt surgery as soon as possible.
Ultrahigh-voltage SiC flip-type n-channel implantation and epitaxial (IE)-IGBTs were developed, and the static and dynamic performance was investigated. A large device (8 mm × 8mm) with a blocking ...voltage greater than 16 kV was achieved, and an on-state current of 20 A was obtained at the low on-state voltage (Von) of 4.8 V. RonAdiff was 23 mΩ·cm2 at Von = 4.8 V. In order to evaluate the switching characteristics of the IE-IGBT, ultrahigh-voltage power modules were assembled. A chopper circuit configuration was used to evaluate the switching characteristics of the IE-IGBT. Smooth turn-off waveforms were successfully obtained at VCE = 6.5 kV and ICE = 60 A in the temperature range from room temperature to 250°C.
Objective Seizure duration has been reported to decrease across a course of electroconvulsive therapy (ECT) (anticonvulsant effect). Because dynamic autonomic activity changes have been described ...during ECT, and are affected by seizure generalization, we examined the relationship between longitudinal autonomic nervous activity changes on a course of ECT and seizure duration. Methods Electroencephalograms (EEG) and electrocardiograms (ECG) of twelve depressive patients were recorded during ECT procedures. The mean heart rate (HR) in 30 s prior to stimulus onset was defined as baseline HR. The TMax peak was designated as the data point with the maximum HR after stimulus onset. T1/2 points were determined as the time point when HR was reduced midway between baseline HR and TMax HR. The changes of EEG seizure duration, TMax , and T1/2 throughout the course of ECT, and their correlations, were examined. Results T1/2 significantly decreased with repetition of ECT. T1/2 was positively correlated to EEG seizure duration. Conclusions The time to return to the baseline from sympathetic nervous activation caused by ECT stimulation is shortened during a course of ECT. Key message Sympathetic nervous activity suppression and an anticonvulsant effect may contribute to the clinical action of ECT.
Objectives: We have previously reported that the level of leucine-rich alpha-2-glycoprotein (LRG) expression is specifically increased in cerebrospinal fluid (CSF) of idiopathic normal pressure ...hydrocephalus (INPH). The objective of this study is to examine the localization of LRG – the cerebral areas where it is expressed.
Method: The histological sections of autopsied brain specimens from ten subjects, five adult cases (mean age 43.6 years; range 34–50 years) and five senile cases (mean age 76.0 years; range 67–88 years) were prepared, multistained with antibodies against human LRG, glial fibrillary acidic protein (GFAP), CD31, and aquaporin-4 (AQP4), and reviewed for the expression sites of LRG.
Results: Immunostains of GFAP and LRG were compared in standard brain specimens from elderly patients. The results indicated that LRG is distributed throughout the entire brain, with especially high expression in the deep cerebral cortex. In addition, the cells that express LRG showed similar morphology to astrocytes. Double staining of CD31 and LRG revealed a significant expression of LRG in the pericapillary regions. The expression was observed in resident astrocytes, as well as in the capillary vessel to which astrocytic processes grow and adhere. When age-related comparisons were made between senile and adult specimens, LRG expression increased with age.
Conclusion: LRG expression in resident astrocytes increased with age.
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