The European iNPH Multicentre Study on the predictive values of resistance to CSF outflow and the CSF Tap Test in patients with idiopathic normal pressure hydrocephalus.
ABSTRACT OBJECTIVE: The objective was to determine the sensitivity, specificity, and positive and negative predictive values of the CSF Tap Test (CSF TT) and resistance to CSF outflow (Rout) for the outcome of shunting in a sample of patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS: 115 patients were included in this European multicentre study. Diagnosis was based on clinical symptoms and signs, and MRI changes. All patients were treated with programmable ventriculoperitoneal shunts and re-examined 12 months after surgery. Outcomes were measures with a newly developed iNPH Scale and the modified Rankin Scale (mRS). Before surgery, a CSF TT and measurement of Rout was performed, with the results blinded to all caregivers. The 12 month outcome was correlated with Rout and the result of the CSF TT. RESULTS: Rout and the results of the CSF TT showed no correlation with outcome measured by either domain, or with total iNPH score or mRS score. Only an increase in the gait task (10 m of walking at free speed) of the CSF TT correlated significantly (r=0.22, p=0.02) with improvement in iNPH score. The positive predictive value of both tests was >90% and the negative predictive value <20%. Rout >12 had an overall accuracy of 65% and the CSF TT 53%. Combining both tests did not improve their predictive power. No correlation was found between Rout and the results of the CSF TT. CONCLUSIONS: Rout and the results of the CSF TT did not correlate with outcome after 12 months. Rout and CSF TT can be used for selecting patients for shunt surgery but not for excluding patients from treatment. TRIAL REGISTRATION: The study has been registered at clinicaltrials.gov, identifier NCT00874198.
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ABSTRACT: We studied the role of cerebrospinal fluid (CSF) tap test at idiopathic normal pressure hydrocephalus (INPH) in improving cerebral blood flow velocity indices by transcranial Doppler (TCD) sonography. Twelve patients with assumed INPH were included in the study. The CSF tap test and INPH grading score was carried out according to the standard protocol. TCD was performed before and after the tap test for assessing blood flow in middle cerebral and anterior cerebral arteries. Five INPH patients (41.7%) had clinical improvement as defined by at least one point reduction in INPH grading scale. The baseline TCD parameters of the middle cerebral artery were significantly higher compared with the control, and those parameters were decreased after tap test in those who improved. Our study showed that improvement in INPH grading score after CSF tap test might correlate with changing in TCD parameter in MCA and TCD parameter might be useful for shunt response in these patients.Iranian Journal of Neurology 10/2014; 13(4):245-9.
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ABSTRACT: Normal pressure hydrocephalus (NPH) is most common in the elderly and has a high co-morbidity with Alzheimer's disease (AD) and cerebrovascular disease (CVD). To understand the relationship between NPH, AD and CVD, we investigated how chronic hydrocephalus impacts brain amyloid-beta peptide (Aβ) accumulation and vascular pathology in an AD transgenic rodent model. Previously we showed that the altered CSF physiology produced by kaolin-hydrocephalus in older wild-type Sprague-Dawley rats increased Aβ and hyperphosphorylated Tau (Silverberg et. al. Brain Res. 2010, 1317:286-296). We postulated that hydrocephalus would similarly affect an AD rat model. Thirty-five transgenic rats (tgAPP21) that express high levels of human APP and naturally overproduce Aβ40 were used. Six- (n = 7) and twelve-month-old (n = 9) rats had hydrocephalus induced by cisternal kaolin injection. We analyzed Aβ burden (Aβ40, Aβ42 and oligomeric Aβ) and vascular integrity (Masson trichrome and Verhoeff-Van Gieson) by immunohistochemistry and chemical staining at 10 weeks (n = 8) and 6 months (n = 5) post hydrocephalus induction. We also analyzed whether the vascular pathology seen in tgAPP21 rats, which develop amyloid angiopathy, was accelerated by hydrocephalus. Age-matched naïve and sham-operated tgAPP21 rats served as controls (n = 19). In hydrocephalic tgAPP21 rats, compared to naïve and sham-operated controls, there was increased Aβ 40 and oligomeric Aβ in hippocampal and cortical neurons at 10 weeks and 6 months post-hydrocephalus induction. No dense-core amyloid plaques were seen, but diffuse Aβ immunoreactivity was evident in neurons. Vascular pathology was accelerated by the induction of hydrocephalus compared to controls. In the six-month-old rats, subtle degenerative changes were noted in vessel walls at 10 weeks post-kaolin, whereas at six months post-kaolin and in the 12-month-old hydrocephalic rats more pronounced amyloid angiopathic changes were seen, with frequent large areas of infarction noted. Kaolin-hydrocephalus can accelerate intraneuronal Aβ40 accumulation and vascular pathology in tgAPP21 rats. In addition, disrupted CSF production and reduced CSF turnover results in impaired Aβ clearance and accelerated vascular pathology in chronic hydrocephalus. The high co-morbidity seen in NPH, AD and CVD is likely not to be an age-related coincidence, but rather a convergence of pathologies related to diminished CSF clearance.
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ABSTRACT: Pseudo-continuous arterial spin labeling (pCASL) measurements were performed in 20 patients with idiopathic normal pressure hydrocephalus (iNPH) to investigate whether cerebral blood flow (CBF) increases during the first 24 hours after a cerebrospinal fluid tap test (CSF TT). Five pCASL magnetic resonance imaging (MRI) scans were performed. Two scans were performed before removal of 40 mL CSF, and the other three at 30 minutes, 4 hours, and 24 hours, respectively after the CSF TT. Thirteen different regions of interest (ROIs) were manually drawn on coregistered MR images. In patients with increased CBF in lateral and frontal white matter after the CSF TT, gait function improved more than it did in patients with decreased CBF in these regions. However, in the whole sample, there was no significant increase in CBF after CSF removal compared with baseline investigations. The repeatability of CBF measurements at baseline was high, with intraclass correlation coefficients of 0.60 to 0.90 for different ROIs, but the median regional variability was in the range of 5% to 17%. Our results indicate that CBF in white matter close to the lateral ventricles plays a role in the reversibility of symptoms after CSF removal in patients with iNPH.Journal of Cerebral Blood Flow & Metabolism advance online publication, 20 August 2014; doi:10.1038/jcbfm.2014.138.Journal of Cerebral Blood Flow & Metabolism 08/2014; 34(11). DOI:10.1038/jcbfm.2014.138 · 5.34 Impact Factor