{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T01:43:25Z","timestamp":1790991805800,"version":"4.1.0"},"reference-count":24,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JNS"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:sec>\n<jats:title>OBJECT<\/jats:title>\n<jats:p>Normal pressure hydrocephalus (NPH) remains most often a clinical diagnosis and has been widely considered responsive to the placement of a cerebrospinal fluid (CSF) shunt. The high incidence of patients with Alzheimer\u2019s disease (AD) with NPH symptoms leads to poorer outcomes than would be expected in patients with NPH alone. This article reviews a series of patients operated on for presumed NPH in whom preoperative high-volume lumbar puncture (HVLP) and intraoperative cortical brain biopsies were performed. The data derived from these procedures were then used to understand the incidence of AD in patients presenting with NPH symptoms and to analyze the efficacy of HVLP in patients with NPH and patients with concurrent AD (NPH+AD). A review of the outcomes of shunt surgery is provided.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>METHODS<\/jats:title>\n<jats:p>The cases of all patients who underwent placement of a CSF shunt for NPH from 1998 to 2013 at the University of Virginia by the senior author were retrospectively reviewed. Patients who underwent HVLP and patients who underwent cortical brain biopsies were stratified based on the biopsy results into an NPH-only group and an NPH+AD group. The HVLP results and outcomes were then compared in these 2 groups.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>RESULTS<\/jats:title>\n<jats:p>From 1998 to 2013, 142 patients underwent shunt operations because of a preoperative clinical diagnosis of NPH. Of the patients with a shunt who had a diagnosis of NPH, 105 (74%) received HVLPs. Of 142 shunt-treated patients with NPH, 27 (19%) were determined to have concomitant Alzheimer\u2019s pathology based on histopathological findings at the time of shunting. Patients who underwent repeat biopsies had an initial positive outcome. After they clinically deteriorated, they underwent repeat biopsies during shunt interrogation, and 13% of the repeat biopsies demonstrated Alzheimer\u2019s pathology. Improvements in gait and cognition did not reach significance between the NPH and NPH+AD groups. In total, 105 patients underwent HVLP before shunt placement. In the NPH cohort, 44.6% of patients experienced improvement in symptoms with HVLP and went on to experience resolution or improvement. In the NPH+AD cohort, this proportion was lower (18.2%), and the majority of patients who experienced symptomatic relief with HVLP actually went on to experience either no change or worsening of symptoms (p = 0.0136).<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>CONCLUSIONS<\/jats:title>\n<jats:p>A high prevalence of AD histopathological findings (19%) occurred in patients treated with shunts for NPH based on cortical brain biopsies performed during placement of CSF shunts. HVLP results alone were not predictive of clinical outcome. However, cortical brain biopsy results and the presence of Alzheimer\u2019s pathology had a strong correlation with success after CSF shunting. Thirteen percent of patients who initially had a normal cortical brain biopsy result had evidence of AD pathology on repeat biopsy, demonstrating the progressive nature of the disease.<\/jats:p><\/jats:sec>","DOI":"10.3171\/2015.2.jns142318","type":"journal-article","created":{"date-parts":[[2015,9,4]],"date-time":"2015-09-04T13:59:26Z","timestamp":1441375166000},"page":"382-388","source":"Crossref","is-referenced-by-count":93,"title":["Concurrent Alzheimer\u2019s pathology in patients with clinical normal pressure hydrocephalus: correlation of high-volume lumbar puncture results, cortical brain biopsies, and outcomes"],"prefix":"10.3171","volume":"124","author":[{"given":"I. Jonathan","family":"Pomeraniec","sequence":"first","affiliation":[{"name":"Departments of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron E.","family":"Bond","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Beatriz","family":"Lopes","sequence":"additional","affiliation":[{"name":"Pathology (Neuropathology), University of Virginia Health Science Center, Charlottesville, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Jane","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1-jns142318","series-title":"Principles and Practice of Pediatric Neurosurgery","author":"Albright","year":"1999"},{"key":"b2-jns142318","series-title":"J Neurol Neurosurg Psychiatry","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1136\/jnnp.2006.095117","article-title":"Idiopathic normal-pressure hydrocephalus: clinical comorbidity correlated with cerebral biopsy findings and outcome of cerebrospinal fluid shunting","volume":"78","author":"Bech-Azeddine","year":"2007"},{"key":"b3-jns142318","series-title":"Alzheimers Dement","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/j.jalz.2010.12.008","article-title":"Frequency of Alzheimer\u2019s disease pathology at autopsy in patients with clinical normal pressure hydrocephalus","volume":"7","author":"Cabral","year":"2011"},{"key":"b4-jns142318","series-title":"Med Hypotheses","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/j.mehy.2004.03.029","article-title":"Unifying concept for Alzheimer\u2019s disease, vascular dementia and normal pressure hydrocephalus - a hypothesis","volume":"63","author":"Chakravarty","year":"2004"},{"key":"b5-jns142318","series-title":"Can J Neurol Sci","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1017\/S0317167100021442","article-title":"Neuropathological changes in chronic adult hydrocephalus: cortical biopsies and autopsy findings","volume":"24","author":"Del Bigio","year":"1997"},{"key":"b6-jns142318","series-title":"J Neurochem","first-page":"880","article-title":"Fate of cerebrospinal fluid-borne amyloid beta-peptide: rapid clearance into blood and appreciable accumulation by cerebral arteries","volume":"67","author":"Ghersi-Egea","year":"1996"},{"key":"b7-jns142318","series-title":"J Neurol Neurosurg Psychiatry","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1136\/jnnp.68.6.778","article-title":"Alzheimer\u2019s disease comorbidity in normal pressure hydrocephalus: prevalence and shunt response","volume":"68","author":"Golomb","year":"2000"},{"key":"b8-jns142318","series-title":"J Neurol Sci","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/0022-510X(65)90016-X","article-title":"The special clinical problem of symptomatic hydrocephalus with normal cerebrospinal fluid pressure. 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