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biopsy_for_idiopathic_normal_pressure_hydrocephalus_diagnosis

Biopsy for Idiopathic normal pressure hydrocephalus diagnosis

Comorbid Alzheimer disease (AD) and Idiopathic normal pressure hydrocephalus (iNPH) is not uncommon, and the likelihood of each is increased with the presence of hypertension and advancing age. AD pathology is present in cortical biopsy of 75% of those iNPH patients with significant dementia at the time of shunt surgery 1).

Brain biopsy from 32 patients with idiopathic normal pressure hydrocephalus were investigated by light and electron microscope. Biopsies were made in 3 points (the cortex, subcortical and periventricular white matter during ventricular catheter positioning).

A number of pathological features of idiopathic normal pressure hydrocephalus were identified. Most frequent were the exhaustion of brain tissue, enlargement of perivascular spaces, aseptic necrosis, and amyloid and Lewy bodies formation.

The changes in brain tissue of patients with idiopathic normal pressure hydrocephalus transform our views on its mechanisms. It becomes clear that idiopathic normal pressure hydrocephalus is part of common neurodegenerative disease process that has characteristic features affecting clinical manifestations of the disease 2).


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. high-volume lumbar puncture (HVLP) results alone were not predictive of clinical outcome. However, cortical brain biopsy results and the presence of Alzheimer's 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 3).


A study population comprised 102 patients with possible NPH with cortical brain biopsies, ventricular and lumbar CSF samples, and DNA available. The final clinical diagnoses were: 53 iNPH (91% shunt-responders), 26 AD (10 mixed iNPH+AD), and 23 others. Biopsy samples were immunostained against Aβ and HPτ. CSF levels of AD-related biomarkers (Aβ42, p-tau, total tau), non-AD-related Aβ isoforms (Aβ38, Aβ40), sAPP isoforms (sAPPα, sAPPβ), proinflammatory cytokines (several interleukins (IL), interferon-gamma, monocyte chemoattractant protein-1, tumor necrosis factor-alpha) and biomarkers of neuronal damage (neurofilament light and myelin basic protein) were measured. All patients were genotyped for APOE.

Lumbar CSF levels of sAPPα were lower (p<0.05) in patients with shunt-responsive iNPH compared to non-iNPH patients. sAPPβ showed a similar trend (p = 0.06). CSF sAPP isoform levels showed no association to Aβ or HPτ in the brain biopsy. Quantified Aβ load in the brain biopsy showed a negative correlation with CSF levels of Aβ42 in ventricular (r = -0.295, p = 0.003) and lumbar (r = -0.356, p = 0.01) samples, while the levels of Aβ38 and Aβ40 showed no correlation. CSF levels of proinflammatory cytokines and biomarkers of neuronal damage did not associate to the brain biopsy findings, diagnosis, or shunt response. Higher lumbar/ventricular CSF IL-8 ratios (p<0.001) were seen in lumbar samples collected after ventriculostomy compared to the samples collected before the procedure.

The role of soluble amyloid precursor protein (sAPP) isoforms in iNPH seems to be independent from the amyloid cascade. No neuroinflammatory background was observed in iNPH or AD 4).


In 28 consecutive patients diagnosed with INPH and shunted according to clinical, radiological and cerebrospinal fluid dynamic criteria, concomitant disorders were carefully registered, with special emphasis on cerebrovascular disease (CVD) and possible Alzheimer's disease. During shunt surgery, a frontal cerebral biopsy specimen was obtained and subsequently analysed for pathological changes.

One or several concurrent disorders were present in 89% of the patients, most often CVD (n = 17) and possible Alzheimer's disease (n = 12), of which eight patients presented both, diagnosed according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association. The shunt success rate was 33%. A clear tendency towards increasing prevalence of CVD or Alzheimer's disease was found in the subgroups with no improvement or clinical deterioration compared with the patients improving after shunt surgery. The presence of CVD tended towards an unfavourable shunt outcome. The pathological parenchymal changes reflected the clinical diagnoses of comorbidity, and were described in about half of the biopsy specimens, with Alzheimer's disease (n = 7) and vascular changes (n = 7) being the most common findings. However, no significant correlation was found with the clinical diagnoses of Alzheimer's disease and CVD. The presence of cerebral comorbidity, whether diagnosed clinically or by brain biopsy, did not preclude clinical improvement after shunt operation.

A high prevalence of CVD and Alzheimer's disease was found in patients shunted for INPH, which was reflected, although less commonly, by similar neuropathological biopsy findings. No significant correlation was found between the presence of comorbidity and shunt outcome. The findings support the perception of INPH as a multiaetiological clinical entity, possibly overlapping pathophysiologically with CVD and Alzheimer's disease 5).

References

1)
Golomb J, Wisoff J, Miller DC, Boksay I, Kluger A, Weiner H, Salton J, Graves W. Alzheimer's disease comorbidity in normal pressure hydrocephalus: prevalence and shunt response. J Neurol Neurosurg Psychiatry. 2000 Jun;68(6):778-81. PubMed PMID: 10811706; PubMed Central PMCID: PMC1736969.
2)
Gavrilov GV, Stanishevskiy AV, Gaydar BV, Paramonova NM, Gaykova ON, Svistov DV. [Pathological changes in human brain biopsies from patients with idiopathic normal pressure hydrocephalus]. Zh Nevrol Psikhiatr Im S S Korsakova. 2019;119(3):50-54. doi: 10.17116/jnevro201911903150. Russian. PubMed PMID: 31089095.
3)
Pomeraniec IJ, Bond AE, Lopes MB, Jane JA Sr. 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. 2016 Feb;124(2):382-8. doi: 10.3171/2015.2.JNS142318. Epub 2015 Sep 4. PubMed PMID: 26339853.
4)
Pyykkö OT, Lumela M, Rummukainen J, Nerg O, Seppälä TT, Herukka SK, Koivisto AM, Alafuzoff I, Puli L, Savolainen S, Soininen H, Jääskeläinen JE, Hiltunen M, Zetterberg H, Leinonen V. Cerebrospinal fluid biomarker and brain biopsy findings in idiopathic normal pressure hydrocephalus. PLoS One. 2014 Mar 17;9(3):e91974. doi: 10.1371/journal.pone.0091974. eCollection 2014. PubMed PMID: 24638077; PubMed Central PMCID: PMC3956805.
5)
Bech-Azeddine R, Høgh P, Juhler M, Gjerris F, Waldemar G. Idiopathic normal-pressure hydrocephalus: clinical comorbidity correlated with cerebral biopsy findings and outcome of cerebrospinal fluid shunting. J Neurol Neurosurg Psychiatry. 2007 Feb;78(2):157-61. Epub 2006 Sep 29. PubMed PMID: 17012342; PubMed Central PMCID: PMC2077673.
biopsy_for_idiopathic_normal_pressure_hydrocephalus_diagnosis.txt · Last modified: 2019/05/16 21:11 by administrador