Associations of intracranial pressure with brain biopsy, radiological findings, and shunt surgery outcome in patients with suspected idiopathic normal pressure hydrocephalus
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It remains unclear how intracranial pressure (ICP) measures are associated with brain biopsies and radiological markers. Here, we aim to investigate associations between ICP and radiological findings, brain biopsies, and shunt surgery outcome in patients with suspected idiopathic normal pressure hydrocephalus (iNPH).
In this study, we retrospectively analyzed data from 73 patients admitted with suspected iNPH to Kuopio University Hospital. Of these patients, 71% underwent shunt surgery. The NPH registry included data on clinical and radiological examinations, 24-h intraventricular pressure monitoring, and frontal cortical biopsy.
The mean ICP and mean ICP pulse wave amplitude were not associated with the shunt response. Aggregations of Alzheimer’s disease (AD)-related proteins (amyloid-β, hyperphosphorylated tau) in frontal cortical biopsies were associated with a poor shunt response (P = 0.014). High mean ICP was associated with Evans’ index (EI; P = 0.025), disproportional sylvian and suprasylvian subarachnoid spaces (P = 0.014), and focally dilated sulci (P = 0.047). Interestingly, a high pulse wave amplitude was associated with AD-related biopsy findings (P = 0.032), but the mean ICP was not associated with the brain biopsy. The ICP was not associated with medial temporal lobe atrophy, temporal horn widths, or white matter changes. ICP B waves were associated with less atrophy of the medial temporal lobe (P = 0.018) and more severe disproportionality between the sylvian and suprasylvian subarachnoid spaces (P = 0.001).
The EI and disproportional sylvian and suprasylvian subarachnoid spaces were associated with mean ICP. Disproportionality was also associated with ICP B waves. These associations, although rather weak, with elevated ICP in 24-h measurements, support their value in iNPH diagnostics and suggest that these radiological markers are potentially related to the pathogenesis of iNPH. Interestingly, our results suggested that elevated pulse wave amplitude might be associated with brain amyloid accumulation.
KeywordsIdiopathic normal pressure hydrocephalus Intracranial pressure Shunt Brain biopsy Alzheimer’s disease Radiology
Idiopathic normal pressure hydrocephalus
Kuopio University Hospital
Mini-Mental State Examination
Magnetic resonance imaging
Normal pressure hydrocephalus
The authors thank Marita Voutilainen, RN, for maintenance of the KUH NPH register and biostatistician Tuomas Selander for statistical assistance.
Compliance with ethical standards
The Fund of Mauri and Sirkka Wiljasalo, KUH VTR Fund, and The Finnish Medical Foundation provided financial support in the form of grant funding. The sponsors had no role in the design or conduct of this research.
Conflicts of interest
All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 13.Hamilton R, Patel S, Lee EB, Jackson EM, Lopinto J, Arnold SE, Clark CM, Basil A, Shaw LM, Xie SX, Grady MS, Trojanowski JQ (2010) Lack of shunt response in suspected idiopathic normal pressure hydrocephalus with Alzheimer disease pathology. Ann Neurol 68:535–540CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Kim E, Lim YJ, Park HS, Kim SK, Jeon YT, Hwang JW, Lee YS, Park HP (2015) The lack of relationship between intracranial pressure and cerebral ventricle indices based on brain computed tomography in patients undergoing ventriculoperitoneal shunt. Acta Neurochir (Wien) 157:257–263CrossRefGoogle Scholar
- 19.Koivisto AM, Alafuzoff I, Savolainen S, Sutela A, Rummukainen J, Kurki M, Jääskeläinen JE, Soininen H, Rinne J, Leinonen V, Kuopio NPH Registry (www.uef.finph) (2013) Poor cognitive outcome in shunt-responsive idiopathic normal pressure hydrocephalus. Neurosurgery 72:1–8
- 24.Laitera T, Kurki MI, Pursiheimo JP, Zetterberg H, Helisalmi S, Rauramaa T, Alafuzoff I, Remes AM, Soininen H, Haapasalo A, Jääskeläinen JE, Hiltunen M, Leinonen V (2015) The expression of transthyretin and amyloid-beta protein precursor is altered in the brain of idiopathic normal pressure hydrocephalus patients. J Alzheimers Dis 48:959–968CrossRefPubMedGoogle Scholar
- 25.Leinonen V, Koivisto AM, Alafuzoff I, Pyykkö OT, Rummukainen J, von Und Zu Fraunberg M, Jääskeläinen JE, Soininen H, Rinne J, Savolainen S (2012) Cortical brain biopsy in long-term prognostication of 468 patients with possible normal pressure hydrocephalus. Neurodegener Dis 10:166–169CrossRefPubMedGoogle Scholar
- 26.Leinonen V, Koivisto AM, Savolainen S, Rummukainen J, Tamminen JN, Tillgren T, Vainikka S, Pyykkö OT, Molsa J, Fraunberg M, Pirttila T, Jääskeläinen JE, Soininen H, Rinne J, Alafuzoff I (2010) Amyloid and tau proteins in cortical brain biopsy and Alzheimer’s disease. Ann Neurol 68:446–453CrossRefPubMedGoogle Scholar
- 28.Malm J, Graff-Radford NR, Ishikawa M, Kristensen B, Leinonen V, Mori E, Owler BK, Tullberg M, Williams MA, Relkin NR (2013) Influence of comorbidities in idiopathic normal pressure hydrocephalus—research and clinical care. A report of the ISHCSF task force on comorbidities in INPH. Fluids Barriers CNS 10:22Google Scholar
- 30.Mori E, Ishikawa M, Kato T, Kazui H, Miyake H, Miyajima M, Nakajima M, Hashimoto M, Kuriyama N, Tokuda T, Ishii K, Kaijima M, Hirata Y, Saito M, Arai H, Japanese Society of Normal Pressure Hydrocephalus (2012) Guidelines for management of idiopathic normal pressure hydrocephalus: second edition. Neurol Med Chir (Tokyo) 52:775–809CrossRefGoogle Scholar
- 35.Scheltens P, Leys D, Barkhof F, Huglo D, Weinstein HC, Vermersch P, Kuiper M, Steinling M, Wolters EC, Valk J (1992) Atrophy of medial temporal lobes on MRI in “probable” Alzheimer’s disease and normal ageing: diagnostic value and neuropsychological correlates. J Neurol Neurosurg Psychiatry 55:967–972CrossRefPubMedPubMedCentralGoogle Scholar