Cognitive, biochemical, and imaging profile of patients suffering from idiopathic normal pressure hydrocephalus

Alzheimers Dement. 2011 Sep;7(5):501-8. doi: 10.1016/j.jalz.2011.01.003. Epub 2011 Jul 14.

Tarnaris A, Toma AK, Pullen E, Chapman MD, Petzold A, Cipolotti L, Kitchen ND, Keir G, Lemieux L, Watkins LD.

Source

Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, London, United Kingdom. andrewtarnaris@gmail.com

Abstract

INTRODUCTION:

It has still not been clearly established whether the cognitive deficits of idiopathic normal pressure hydrocephalus (iNPH) are caused by a disturbance in cerebrospinal fluid (CSF) dynamics or an underlying metabolic disturbance.

OBJECTIVE:

To identify the possible associations between biochemical markers, the neuroimaging characteristics, and cognitive deficits of patients undergoing investigations for possible iNPH.

METHODS:

A CSF sample obtained during a lumbar puncture from 10 patients with iNPH was analyzed for several biochemical markers (lactate, 8-isoprostane, vascular endothelial growth factor [VEGF], neurofilament heavy protein, glial fibrillary acidic protein, amyloid beta 1-42, and total tau). All patients underwent a battery of neuropsychological testing and imaging as part of their selection process for their suitability for CSF diversion surgical procedure. Volumetric analysis of imaging was carried out measuring the ventricular volume (VV), intracranial volume (ICV), periventricular lucencies, deep white matter hyperintensities, and white matter (WM) volume, as well as their ratios.

RESULTS:

A significant negative correlation of preoperative symptom duration and total tau levels (R = -0.841, P = .002) was found. There was a significant positive correlation (R = 0.648, P = .043) between the levels of VEGF and the VV/ICV ratio. There was a significant positive correlation of the levels of glial fibrillary acidic protein and the VV/deep white matter hyperintensities ratio (R = 0.828, P = .006). A significant negative correlation was observed between the levels of neurofilament heavy protein and the VV/ICV ratio (R = -0.657, P = .039) and the WM volume (R = -0.778, P = .023). Lactate levels were lower for patients performing in the normal range on the Recognition Memory Test for faces. Patients who performed better in the Recognition Memory Test words test had higher ICV volumes. All the patients in this study showed below normal performance when the subcortical function was assessed.

CONCLUSION:

The positive correlation of VEGF with the severity of ventriculomegaly may indicate that this is because of the transmantle pressure gradient; this response may not be because of hypoxia but represents an attempt at neuroregeneration. The degree of reactive gliosis correlates inversely with the severity of WM lesions. Neuronal degeneration is negatively correlated with the volume of the WM in these patients. The small association of volumetry and the cognitive profile of these patients may be consistent with a direct biochemical disturbance being responsible for the cognitive deficit observed. Ongoing studies with set protocols for neuropsychological assessment and volumetric analysis are warranted to further elucidate on the preliminary results of the current study

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Use of cerebrospinal fluid amyloid-β and total tau protein to predict favorable surgical outcomes in patients with idiopathic normal pressure hydrocep

http://thejns.org/doi/abs/10.3171/2011.2.JNS101316 Andrew Tarnaris, M.R.C.S.1, Ahmed. K. Toma, F.R.C.S.(NS)1, Miles D. Chapman, Ph.D.2, Geoff Keir, Ph.D.2, Neil D. Kitchen, M.D., F.R.C.S.(SN)1, and Laurence D. Watkins, M.A., F.R.C.S.(SN)1 1Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery; and 2Department of Neuroimmunology, Institute of Neurology, Queen Square, London, United Kingdom Abbreviations used in this paper: Aβ1–42 = amyloid-β 1–42; AD = Alzheimer dementia; ELISA = enzyme-linked immunosorbent assay; iNPH = idiopathic normal pressure hydrocephalus. Address correspondence to: Andrew Tarnaris, M.R.C.S., Department of Neurosurgery, National Hospital for Neurology & Neurosurgery, Box 32, Queen Square, London WC1N 3BG. email: andrewtarnaris@gmail.com. Please include this information when citing this paper: published online March 25, 2011; DOI: 10.3171/2011.2.JNS101316. DOI: 10.3171/2011.2.JNS101316 Object The prognostic value of CSF biomarkers in patients with idiopathic normal pressure hydrocephalus (iNPH) has not been adequately studied to date. The aim of this study was to identify CSF markers of favorable surgical outcome in patients with iNPH undergoing the insertion of a ventriculoperitoneal shunt. Methods Ventricular CSF was collected intraoperatively from 22 patients with iNPH and enzyme-linked immunosorbent assay was used to analyze the levels of amyloid-β 1–42 (Aβ1–42) and total tau protein. The Black grading scale was used to assess outcomes at 6 months. Receiver operating characteristic (ROC) curves were obtained and discriminant function analysis was undertaken to provide sensitivity and specificity figures for each marker as well as their combination. Results The mean age of the patients was 71.45 years (± 9.5 years [SD]). Follow-up was achieved in 21 patients. Seventeen patients had a favorable outcome and 4 patients had unfavorable outcome at 6 months. An Aβ1–42 level of 180 pg/ml had a sensitivity of 35% and a specificity of 20% for predicting a favorable outcome at 6 months. A total tau level of 767 pg/ml will have a sensitivity of 17% and a specificity of 20% for predicting a favorable outcome at 6 months. A combination of Aβ1–42 and total tau levels predicted favorable outcomes with a sensitivity of 80% and specificity of 82.4%. Conclusions In this pilot study a combination of Aβ1–42 levels and total tau protein levels predicted favorable surgical outcomes at 6 months with adequate accuracy to be of clinical use. Further study in a larger group with longer follow-up is warranted. KEYWORDS:hydrocephalus; normal pressure hydrocephalus; biomarkers; outcome; tau protein; amyloid-β.

Is there a difference in outcomes of patients with idiopathic intracranial hypertension with the choice of cerebrospinal fluid diversion site

Clin Neurol Neurosurg. 2011 Mar 14. [Epub ahead of print]
Is there a difference in outcomes of patients with idiopathic intracranial hypertension with the choice of cerebrospinal fluid diversion site: A single centre experience.
Tarnaris A, Toma AK, Watkins LD, Kitchen ND.
Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, Queen Square, London WC 1N 3BG, UK.
Abstract
The visual and headache outcomes in patients with idiopathic intracranial hypertension (IIH) undergoing cerebrospinal fluid diversion with a lumboperitoneal (LPS) or ventriculoperitoneal shunting (VPS) have not been well reported. The aims of this study were to: (a) to assess outcomes of CSF diversion in IIH, (b) to understand influence of the type of shunt in outcomes, and (c) to understand factors predisposing in shunt failure.
METHODS: The medical records of 34 patients who underwent cerebrospinal fluid diversion (CSFD) between 1996 and 2007 were retrieved and epidemiological and clinical data was collected.
RESULTS: The mean age was 35 (±7.9) years. Thirty-four patients underwent 63 shunt placements in total. 85% follow-up was achieved. The mean follow-up for the entire group was 28.9 (±31.8) months. Headaches improved more than visual disturbances. There was no significant difference between the groups that received a VPS and those receiving an LPS in both headache and visual outcomes. The rate of complications was 20.5% and the need for revision was 35% for the whole group. Patients with LPS suffered more complications and first time revisions than patients with VPS. No factor recorded could predict the need for revision or final outcomes. The shunts of patients receiving a VPS tend to survive longer than those receiving primarily an LPS, however the difference is not statistically significant.
CONCLUSIONS: Predicting which patients will improve is not possible at present. The influence of site diversion is not critical but patients with VPS have less complications and revisions than those receiving a LPS.

Idiopathic Normal Pressure Hydrocephalus: Update and Practical Approach on Diagnosis and Management

Andrew Tarnaris, MRCS,* and Michael A. Williams, MD, FAANw

The syndrome of idiopathic normal pressure hydrocephalus was first described in 1965, but 45 years later controversies still exist with regard to its cause, progression, differential diagnosis, and best treatment strategies. Its incidence may be underestimated and its importance increasing because of the aging population. The authors review current literature and offer an update on contemporary knowledge as well as a practical approach to diagnosis and management of the condition for the neurologists and neurosurgeons who encounter such patients.

(Neurosurg Q 2011;21:72–81)

http://journals.lww.com/neurosurgery-quarterly/Abstract/2011/02000/Idiopathic_Normal_Pressure_Hydrocephalus___Update.16.aspx

Rostrocaudal Dynamics of CSF Biomarkers.

http://www.springerlink.com/content/b3834t464607028x/
Neurochem Res. 2010 Dec 30. [Epub ahead of print]
Rostrocaudal Dynamics of CSF Biomarkers.
Tarnaris A, Toma AK, Chapman MD, Petzold A, Keir G, Kitchen ND, Watkins LD.
The Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, Box 32, Queen Square, London, WC, 1N 3BG, UK, andrewtarnaris@gmail.com.
Abstract
The rostrocaudal gradient (RCG) of markers present in cerebrospinal fluid (CSF) has not been studied adequately due to lack of appropriate control populations and ethical restrictions. The aim of this study is to understand the rostrocaudal gradient of CSF biomarkers. We contacted a study comparing CSF levels of seven biomarkers from cisternal (rostral) and lumbar (caudal) CSF obtained from patients with trigeminal neuralgia and tension-type headache. The RCGs of CSF/serum albumin ratio, 8-isoprostane. GFAP, total tau and beta amyloid protein were higher than one. The RCGs of lactate, VEGF and the heavy chain of neurofilament protein were lower than one. The study provides new values for several commonly examined markers of cisternal CSF. Knowledge of the RCG gradient of different CSF markers is important in interpreting studies reporting ventricular CSF values.