Acta Neurochirurgica

, Volume 159, Issue 1, pp 51–61 | Cite as

Associations of intracranial pressure with brain biopsy, radiological findings, and shunt surgery outcome in patients with suspected idiopathic normal pressure hydrocephalus

  • Maria KojoukhovaEmail author
  • Krista-Irina Vanha
  • Matti Timonen
  • Anne M. Koivisto
  • Ossi Nerg
  • Jaana Rummukainen
  • Tuomas Rauramaa
  • Ritva Vanninen
  • Juha E. Jääskeläinen
  • Anna Sutela
  • Ville Leinonen
Clinical Article - Neurosurgical Anatomy



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.


Idiopathic normal pressure hydrocephalus Intracranial pressure Shunt Brain biopsy Alzheimer’s disease Radiology 


Amyloid beta


Alzheimer’s disease


Cerebrospinal fluid


Computed tomography


Evans’ index


Hyperphosphorylated tau


Intracranial pressure


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.

Ethical approval

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

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Bateman GA (2004) Pulse wave encephalopathy: a spectrum hypothesis incorporating Alzheimer’s disease, vascular dementia and normal pressure hydrocephalus. Med Hypotheses 62:182–187CrossRefPubMedGoogle Scholar
  2. 2.
    Borgesen SE, Gjerris F (1987) Relationships between intracranial pressure, ventricular size, and resistance to CSF outflow. J Neurosurg 67:535–539CrossRefPubMedGoogle Scholar
  3. 3.
    Czosnyka M, Pickard JD (2004) Monitoring and interpretation of intracranial pressure. J Neurol Neurosurg Psychiatry 75:813–821CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Eide PK (2008) Demonstration of uneven distribution of intracranial pulsatility in hydrocephalus patients. J Neurosurg 109:912–917CrossRefPubMedGoogle Scholar
  5. 5.
    Eide PK (2006) Intracranial pressure parameters in idiopathic normal pressure hydrocephalus patients treated with ventriculo-peritoneal shunts. Acta Neurochir (Wien) 148:21–29CrossRefGoogle Scholar
  6. 6.
    Eide PK (2006) A new method for processing of continuous intracranial pressure signals. Med Eng Phys 28:579–587CrossRefPubMedGoogle Scholar
  7. 7.
    Eide PK, Sorteberg W (2016) Outcome of surgery for idiopathic normal pressure hydrocephalus: role of preoperative static and pulsatile intracranial pressure. World Neurosurg 86:186–193CrossRefPubMedGoogle Scholar
  8. 8.
    Eide PK, Sorteberg W (2010) Diagnostic intracranial pressure monitoring and surgical management in idiopathic normal pressure hydrocephalus: a 6-year review of 214 patients. Neurosurgery 66:80–91CrossRefPubMedGoogle Scholar
  9. 9.
    Eide PK, Stanisic M (2010) Cerebral microdialysis and intracranial pressure monitoring in patients with idiopathic normal-pressure hydrocephalus: association with clinical response to extended lumbar drainage and shunt surgery. J Neurosurg 112:414–424CrossRefPubMedGoogle Scholar
  10. 10.
    Evans WA (1942) An encephalographic ratio for estimating ventricular enlargement and cerebral atrophy. Arch Neurol Psych 47:931CrossRefGoogle Scholar
  11. 11.
    Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA (1987) MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJR Am J Roentgenol 149:351–356CrossRefPubMedGoogle Scholar
  12. 12.
    Foss T, Eide PK, Finset A (2007) Intracranial pressure parameters in idiopathic normal pressure hydrocephalus patients with or without improvement of cognitive function after shunt treatment. Dement Geriatr Cogn Disord 23:47–54CrossRefPubMedGoogle Scholar
  13. 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
  14. 14.
    Hashimoto M, Ishikawa M, Mori E, Kuwana N, Study of INPH on neurological improvement (SINPHONI) (2010) Diagnosis of idiopathic normal pressure hydrocephalus is supported by MRI-based scheme: a prospective cohort study. Cerebrospinal Fluid Res 7:18CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Holodny AI, Waxman R, George AE, Rusinek H, Kalnin AJ, de Leon M (1998) MR differential diagnosis of normal-pressure hydrocephalus and Alzheimer disease: significance of perihippocampal fissures. AJNR Am J Neuroradiol 19:813–819PubMedGoogle Scholar
  16. 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
  17. 17.
    Kitagaki H, Mori E, Ishii K, Yamaji S, Hirono N, Imamura T (1998) CSF spaces in idiopathic normal pressure hydrocephalus: morphology and volumetry. AJNR Am J Neuroradiol 19:1277–1284PubMedGoogle Scholar
  18. 18.
    Klinge PM, Samii A, Niescken S, Brinker T, Silverberg GD (2006) Brain amyloid accumulates in aged rats with kaolin-induced hydrocephalus. Neuroreport 17:657–660CrossRefPubMedGoogle Scholar
  19. 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
  20. 20.
    Koivisto AM, Kurki MI, Alafuzoff I, Sutela A, Rummukainen J, Savolainen S, Vanninen R, Jääskeläinen JE, Soininen H, Leinonen V (2016) High risk of dementia in ventricular enlargement with normal pressure hydrocephalus related symptoms1. J Alzheimers Dis 52:497–507CrossRefPubMedGoogle Scholar
  21. 21.
    Kojoukhova M, Koivisto AM, Korhonen R, Remes AM, Vanninen R, Soininen H, Jaaskelainen JE, Sutela A, Leinonen V (2015) Feasibility of radiological markers in idiopathic normal pressure hydrocephalus. Acta Neurochir (Wien) 157:1709–1718CrossRefGoogle Scholar
  22. 22.
    Kondziella D, Sonnewald U, Tullberg M, Wikkelso C (2008) Brain metabolism in adult chronic hydrocephalus. J Neurochem 106:1515–1524CrossRefPubMedGoogle Scholar
  23. 23.
    Krauss JK, Droste DW, Vach W, Regel JP, Orszagh M, Borremans JJ, Tietz A, Seeger W (1996) Cerebrospinal fluid shunting in idiopathic normal-pressure hydrocephalus of the elderly: effect of periventricular and deep white matter lesions. Neurosurgery 39:292–299CrossRefPubMedGoogle Scholar
  24. 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. 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. 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
  27. 27.
    Lundberg N (1960) Continuous recording and control of ventricular fluid pressure in neurosurgical practice. Acta Psychiatr Scand Suppl 36:1–193PubMedGoogle Scholar
  28. 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
  29. 29.
    Marmarou A, Black P, Bergsneider M, Klinge P, Relkin N, International NPH Consultant Group (2005) Guidelines for management of idiopathic normal pressure hydrocephalus: progress to date. Acta Neurochir Suppl 95:237–240CrossRefPubMedGoogle Scholar
  30. 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
  31. 31.
    Pomeraniec IJ, Bond AE, Lopes MB, Jane JAS (2016) Concurrent Alzheimer’s pathology in patients with clinical normal pressure hydrocephalus: correlation of high-volume lumbar puncture results, cortical brain biopsies, and outcomes. J Neurosurg 124:382–388CrossRefPubMedGoogle Scholar
  32. 32.
    Relkin N, Marmarou A, Klinge P, Bergsneider M, Black PM (2005) Diagnosing idiopathic normal-pressure hydrocephalus. Neurosurgery 57:S4–S16PubMedGoogle Scholar
  33. 33.
    Savolainen S, Hurskainen H, Paljarvi L, Alafuzoff I, Vapalahti M (2002) Five-year outcome of normal pressure hydrocephalus with or without a shunt: predictive value of the clinical signs, neuropsychological evaluation and infusion test. Acta Neurochir (Wien) 144:515–523CrossRefGoogle Scholar
  34. 34.
    Savolainen S, Paljarvi L, Vapalahti M (1999) Prevalence of Alzheimer’s disease in patients investigated for presumed normal pressure hydrocephalus: a clinical and neuropathological study. Acta Neurochir (Wien) 141:849–853CrossRefGoogle Scholar
  35. 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
  36. 36.
    Spiegelberg A, Preuß M, Kurtcuoglu V (2016) B-waves revisited. Interdisc Neurosurg 6:13–17CrossRefGoogle Scholar
  37. 37.
    Toma AK, Holl E, Kitchen ND, Watkins LD (2011) Evans’ index revisited: the need for an alternative in normal pressure hydrocephalus. Neurosurgery 68:939–944PubMedGoogle Scholar
  38. 38.
    Tullberg M, Jensen C, Ekholm S, Wikkelso C (2001) Normal pressure hydrocephalus: vascular white matter changes on MR images must not exclude patients from shunt surgery. AJNR Am J Neuroradiol 22:1665–1673PubMedGoogle Scholar
  39. 39.
    Virhammar J, Laurell K, Cesarini KG, Larsson EM (2014) Preoperative prognostic value of MRI findings in 108 patients with idiopathic normal pressure hydrocephalus. AJNR Am J Neuroradiol 35:2311–2318CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Maria Kojoukhova
    • 1
    Email author
  • Krista-Irina Vanha
    • 1
  • Matti Timonen
    • 1
  • Anne M. Koivisto
    • 2
    • 3
  • Ossi Nerg
    • 2
    • 3
  • Jaana Rummukainen
    • 4
  • Tuomas Rauramaa
    • 4
    • 5
  • Ritva Vanninen
    • 6
  • Juha E. Jääskeläinen
    • 1
  • Anna Sutela
    • 6
  • Ville Leinonen
    • 1
  1. 1.Neurosurgery of NeuroCenterKuopio University Hospital and University of Eastern FinlandKuopioFinland
  2. 2.Unit of Neurology, Institute of Clinical MedicineUniversity of Eastern FinlandKuopioFinland
  3. 3.Neurology of NeuroCenterKuopio University HospitalKuopioFinland
  4. 4.Department of PathologyKuopio University HospitalKuopioFinland
  5. 5.Institute of Clinical Medicine-PathologyUniversity of Eastern FinlandKuopioFinland
  6. 6.Department of RadiologyKuopio University Hospital and University of Eastern FinlandKuopioFinland

Personalised recommendations