Tarnaris, A; (2012) Biomarkers in patients with idiopathic normal pressure hydrocephalus. Doctoral thesis , UCL (University College London).

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Abstract

Idiopathic normal pressure hydrocephalus (iNPH) is a condition affecting a small percentage of the elderly population; however it is the only known treatable cause of dementia. Surgical cerebrospinal fluid (CSF) diversion is the only known treatment for the condition today. However, such a procedure is not to be offered lightly and any expected benefit has to balance the associated surgical risks. The prognosis of a favourable surgical outcome has been problematic since the conception of the syndrome. None of current prognostic tests reaches 100% sensitivity or specificity and it is felt that there might be a need for a combination of tests, rather than a single one to maximize the chances of selecting the right patients to offer a surgical CSF diversion procedure. Biomarkers are biological substances that may act as surrogate markers of response to a treatment or to characterise a disease’s progression over time. The aim of this study was to identify CSF markers of favourable surgical outcome in patients with iNPH undergoing the insertion of a ventriculoperitoneal shunt (VPS). We first describe the effects of external lumbar drainage (ELD) on the CSF biochemistry of these patients. Correlations are made with imaging data obtained from volumetric analysis and neuropsychological tests in order to obtain a complete profile of these patients. The rostrocaudal gradients of the CSF markers examined are reported showcasing the need to understand that commonly reported values from lumbar CSF do not necessarily reflect pathological changes occurring at cerebral level. Finally, we report on the individual as well as combined prognostic value of 7 CSF markers on surgical outcomes at 6 months. The pathophysiological significance of these markers is discussed individually. It is concluded that the combined power of total tau and Aβ 1-42 may be useful in predicting favourable surgical outcomes at 6 months; further studies applying the findings in a larger cohort and correlating findings with longer outcomes are warranted to enhance the clinical application. The biochemical profile of patients with iNPH appears unique and different than patients with Alzheimer’s dementia or control subjects.

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