Cortical Brain Biopsy in Long-Term Prognostication of 468 Patients with Possible Normal Pressure Hydrocephalus

Abstract

Normal pressure hydrocephalus (NPH) can be alleviated by cerebrospinal fluid shunting but the differential diagnosis and patient selection are challenging. Intraventricular intracranial pressure monitoring as part of the diagnostic workup as well as shunting enable to obtain cortical brain biopsies to detect amyloid-β (Aβ) and hyperphosphorylated tau (HPτ), the hallmark lesions of Alzheimer’s disease (AD). In possible NPH, Aβ alone indicates an increased risk of AD and when present with HPτ probable AD, but the effect of those brain lesions on survival is not known. The aim of this study was to evaluate the predictive value of brain biopsy for the long-term outcome of possible NPH. Between 1991 and 2006, the Neurosurgery Department of the Kuopio University Hospital evaluated 468 patients for possible NPH by intraventricular intracranial pressure monitoring and frontal cortical brain biopsy immunostained against Aβ and HPτ. All patients were followed up until the end of 2008 (n = 201) or death (n = 267) with a median follow-up of 4.6 years (range 0–17). Logistic regression analysis with Cox models was applied. Out of the 468 cases, Aβ was detected in 197 (42%) cortical biopsies, and together with HPτ in 44 (9%). Aβ alone indicated increased risk of AD and with HPτ probable AD, but it did not affect survival. Vascular aetiology was the most frequent cause of death. Cortical biopsy findings indicate that NPH is at present a heterogeneous syndrome and has notable overlapping with AD. Brain biopsy did not predict survival but may open a novel research window to study the pathobiology of neurodegeneration.

Soluble Amyloid-beta Aggregates from Human Alzheimer’s Disease Brains

“…To date, we and others have not been able to detect soluble Aβ aggregates in human cerebrospinal fluid4049, though some groups have done so505152. Assessments of brain biopsy tissue from patients undergoing normal pressure hydrocephalus surgery, nearly half of whom may also have Aβ pathology53, represent a logical direction for addressing potential post-mortem artifacts. Direct detection in the brain using molecularly specific electrode technology may represent a novel approach54.…”

Frontotemporal dementia as a comorbidity to idiopathic normal pressure hydrocephalus (iNPH): a short review of literature and an unusual case

“…There is also increasing evidence that iNPH may have a genetic component [27–31]. We have previously observed that over 40% of iNPH patients present, on their cortical biopsies, with either beta-amyloid, hyperphosphorylated tau protein or both [8]. It has been reported that beta-amyloid and hyperphosphorylated tau protein accumulation in the brain is increased in Kaolin-aged hydrocephalic rats and it has been hypothesized that the accumulation is due to decreased CSF clearance [32, 33].…”

“…Amyloid beta plaques and hyperphosphorylated tau-protein inclusions have been frequently identified in neuropathological studies and studies using frontal cortical biopsies in iNPH [6–8]. …”

MR Elastography Demonstrates Increased Brain Stiffness in Normal Pressure Hydrocephalus

“…Multiple overlapping signs and symptoms between different types of cognitive impairment such as NPH, Alzheimer's disease and vascular dementia [2-4] create diagnostic challenges in patients with cognitive impairment. This motivates the development and investigation of novel noninvasive imaging techniques to serve as diagnostic tools for identifying patients with NPH.…”