Utjecaj vanjske lumbalne drenaže na tlak i volumen cerebrospinalne tekućine, koncentracije amiloida beta i tau proteina i na klinički status bolesnika s idiopatskim normotenzivnim hidrocefalusom

doctoral thesis

• Title (english): The influence of external lumbar drainage on cerebrospinal fluid pressure and volume, amyloid beta and tau protein concentrations, and on the clinical status of patients with idiopathic normal pressure hydrocephalus
• Author: Klara Brgić Mandić
• Mentor: Marijan Klarica (mentor)
• Mentor: Goran Mrak (komentor)
• Committee member: Milan Radoš (predsjednik povjerenstva)
• Committee member: Ivana Jurjević (član povjerenstva)
• Committee member: Miroslav Vukić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Neurology); Zagreb
• Defense date and country: 2024-09-24, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Neurology
• Universal decimal classification (UDC): 61 - Medical sciences

Abstract

Patofiziologija normotenzivnog hidrocefalusa (NPH) nije jasna, te se danas ispituju razni prognostički čimbenici na osnovu kojih bi se mogli odabrati bolesnici za operacijsko liječenje. Cilj ovog istraživanja je bio ispitati po prvi put da li promjene kranijskog i spinalnog volumena cerebrospinalne tekućine (CST) mjenjaju intrakranijsku hidrodinamiku i koncentracije biomarkera, te intrakranijski tlak uz poboljšanje kliničkog stanja bolesnika koje opravdava operacijsko postavljanje trajne drenaže. Dvadeset bolesnika s kliničkom i neuroradiološkom sumnjom na NPH su bili podvrgnuti vanjskoj lumbalnoj drenaži tijekom razdoblja od 72 h, uz praćenje promjena koncentracije biomarkera u CST-u i intrakranijskog tlaka, te mjerenje volumena CST-a u kraniospinalnom prostoru prije i nakon drenaže. Kod 10 bolesnika došlo je do kliničkog poboljšanja. Rezultati su pokazali da je sposobnost regulacije tlaka CST-a s promjenama volumena znatno smanjena u bolesnika s negativnim kliničkim odgovorom. MR volumetrijom uočeno je kako volumen CST-a u kraniju čini oko 20% ukupnog intrakranijskog volumena, te da je taj volumen kao i ukupni kraniospinalni volumen veći u bolesnika koji imaju pozitivan klinički odgovor na produženu lumbalnu drenažu. Zbroj ukupnog volumena CST-a u kraniju i u spinalnom prostoru ukazuje da taj volumen iznosi oko 466 ml u odraslih osoba što je znatno više nego se to do sada mislilo čak i kad se umanji volumen za 150 ml što predstavlja prosječno povećanje komora kod NPH bolesnika. Promjene koncentracije odabranih biomarkera (amiloid β, ukupni i fosforilirani tau proteini) iz uzoraka CST-a u tri vremenske točke (0, 36 i 72 h) tijekom drenaže povezane su s promjenom kliničkog stanja. Pokazano je kako postupni porast koncetracije Aβ1-42 koji se događa tijekom trodnevne drenaže CST-a predstavlja mogući pozitivni prognostički čimbenik za postavljanje trajne CST drenaže u bolesnika s NPH-om.

Abstract (english)

The pathophysiology of normal pressure hydrocephalus (NPH) is not clear, and various prognostic factors are currently being investigated that could facilitate the selection of patients who would benefit from surgical treatment. This research aimed to examine for the first time whether changes in cranial and spinal volume of cerebrospinal fluid (CSF) influence intracranial hydrodynamics and biomarker concentrations, as well as intracranial pressure while improving the patient's clinical condition, which justifies surgical placement of permanent drainage. Twenty patients with clinical and euroradiological signs of NPH underwent external lumbar drainage during a period of 72 h. During this period we monitored changes in the concentration of biomarkers in the CSF and intracranial pressure, and also measured the volume of CSF in the craniospinal space before and after drainage. Clinical improvement was observed in 10 patients. The results showed that the ability to regulate CSF pressure with volume changes was significantly reduced in patients with negative clinical response. MRI volumetry showed that intracranial CSF accounts for 20% of the total intracranial volume, and that this CSF
volume, as well as the total craniospinal volume, is greater in patients who have a positive clinical response (responders) to extended lumbar drainage. The sum of the total volume of the CSF in the cranium and in the spinal space indicates that this volume is about 466 ml in adults, which is significantly higher than previously thought, even when the volume is reduced by 150 ml, which represents the average increase in the ventricles in NPH patients. Changes in the concentration of selected biomarkers (amyloid β, total, and phosphorylated tau proteins) from CSF samples at three-time points (0, 36, and 72 h) during drainage are associated with changes in the clinical condition. The gradual increase in Aβ1-42 concentration that occurs during the three-day CSF drainage represents a possible positive prognostic factor for the placement of permanent CSF drainage in patients with NPH.

• Keywords: cerebrospinalna tekućina; normotenzivni hidrocefalus; intrakranijski i spinalni volumen CST-a; intrakranijski tlak; vanjska lumbalna drenaža; biomarkeri u CST-u
• Keywords (english): cerebrospinal fluid; normal pressure hydrocephalus; intracranial and intraspinal CSF volume; intracranial pressure; external lumbar drainage; CSF biomarkers
• Language: croatian
• URN:NBN: urn:nbn:hr:105:187641
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Type of resource: Text
• Extent: 85 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-10-01 09:19:25