Σποραδικές μελέτες περιγράφουν την προσωρινή εξωτερική οσφυϊκή παροχέτευση του ΕΝΥ, ως μία δοκιμασία υψηλής ακριβείας όσον αφορά στην πρόβλεψη του κλινικού αποτελέσματος μετά από κοιλιοπεριτοναϊκή παροχέτευση στους ασθενείς με ΥΦΠ. Παρόλα αυτά, σε μία πιο πρόσφατη μελέτη από τους Walchenbach και συνεργάτες, εκτιμήθηκε ότι η θετική προγνωστική αξία της ΕΟΠ ήταν υψηλή, ενώ η αρνητική χαμηλή. Δια ταύτα, πραγματοποιήσαμε μία προοπτική μελέτη με σκοπό να εκτιμήσουμε την προγνωστική αξία μιάς προσωρινής εξωτερικής οσφυικής παροχέτευσης (ΕΟΠ), η οποία ρυθμίζει την εκροή ΕΝΥ μέσω μιάς βαλβίδας μέσης πίεσης μονόδρομης ροής, σε ασθενείς με υδροκέφαλο φυσιολογικής πίεσης (ΥΦΠ). Είκοσι επτά 27 ασθενείς με ΥΦΠ εισήχθησαν στη Νευροχειρουργική Κλινική του ΠΓΝΠ και υπεβλήθησαν σε τοποθέτηση προσωρινής εξωτερικής οσφυικής παροχέτευσης (ΕΟΠ), η οποία ρυθμίζει την εκροή ΕΝΥ μέσω μιάς βαλβίδας μέσης πίεσης, για 5 ημέρες. 22 ασθενείς υπεβλήθησαν τελικά σε κοιλιοπεριτοναϊκή παροχέτευση με βαλβίδα μέσης πίεσης, βασιζόμενοι σε κλινικά και ακτινολογικά κριτήρια, ανεξαρτήτως του αποτελέσματος της ΕΟΠ. Κλινική εκτίμηση των διαταραχών της βάδισης, της ούρησης και της νόησης, όπως επίσης και ακτινολογική εκτίμηση, πραγματοποιήθηκε προ και μετά την δοκιμασία της ΕΟΠ καθώς και 3 μήνες μετά την ΚΠΠ. Είκοσι δύο 22 ασθενείς υπεβλήθησαν τελικά σε κοιλιοπεριτοναϊκή παροχέτευση και πληρούσαν τα κριτήρια για να συμπεριληφθούν τελικά στη μελέτη. Χρησιμοποιώντας ένα εγκεκριμένο σύστημα βαθμολόγησης, η συνολική βελτίωση μετά τη δοκιμασία ΕΟΠ συσχετιζόταν καλά με τη βελτίωση 3 μήνες μετά την μόνιμη ΚΠΠ. (Spearman’ s rho = 0,462, p=0,03). Όταν θεωρήσαμε κάθε βαθμό βελτίωσης ως θετική ανταπόκριση, η δοκιμασία ΕΟΠ-βαλβίδας μέσης πίεσης είχε υψηλή θετική προγνωστική αξία για κάθε μία ανεξάρτητη κλινική παράμετρο (διαταραχές της βάδισης 94%, 95% CI 71%-100%, ακράτεια στην ούρηση 100%, 95% CI 66%-100%, διαταραχές της νόησης 100%, 95% CI 66-100%), ενώ η αρνητική προγνωστική αξία ήταν χαμηλή (<50%) εκτός από τις διαταραχές της νόησης (85%, 95% CI 55%-98%). Η ανωτέρω μελέτη συμπεραίνει ότι η δοκιμασία της ΕΟΠ-βαλβίδας μέσης πίεσης, θα πρέπει να θεωρείται ένα αξιόπιστο κριτήριο για την προεγχειρητική επιλογή υδροκεφαλικών ασθενών φυσιολογικής πίεσης που βελτιώνονται κλινικά μετά την τοποθέτηση ΚΠΠ. Σε περίπτωση αρνητικής δοκιμασίας ΕΟΠ-βαλβίδας μέσης πίεσης, θα πρέπει να διενεργείται περαιτέρω διερεύνηση με επιπρόσθετες διαγνωστικές δοκιμασίες. / Although sporadic studies have described temporary external cerebrospinal fluid (CSF) lumbar drainage as a highly accurate test in predicting the outcome after ventricular shunting in normal pressure hydrocephalus (NPH) patients, a more recent study reports that the positive predictive value of external lumbar drainage (ELD) is high but the negative predictive value is deceptively low. Therefore, we conducted a prospective study in order to evaluate the predictive value of a continuous ELD, with CSF outflow controlled by medium pressure valve, in NPH patients. Twenty-seven patients with presumed NPH were admitted to our department and CSF drainage was carried out by a temporary (ELD), with CSF outflow controlled by medium pressure valve for five days. Twenty-two patients received a ventriculo¬peritoneal shunt with medium pressure valve based upon preoperative clinical and radiographic criteria of NPH, regardless of ELD outcome. Clinical evaluation of gait disturbances, urinary incontinence and mental status, and radiological evaluation with brain CT was performed prior to and after ELD test, as well as three months after shunting. Twenty-two patients were finally shunted and included in this study. In a three-month follow-up, using a previously validated score system, overall improvement after permanent shunting correlated well with improvement after ELD test (Spearman’s rho=0.462, p=0.03). When considering any degree of improvement as a positive response, ELD test yielded high positive predictive values for all individual parameters (gait disturbances 94%, 95% CI 71%-100%, urinary incontinence 100%, 95% CI 66%-100%, and mental status 100%, 95% CI 66%-100%) but negative predictive values were low (<50%) except for cognitive impairment (85%, 95% CI 55%-98%). This study suggests that a positive ELD-valve system test should be considered a reliable criterion for preoperative selection of shunt-responsive NPH patients. In case of a negative ELD-valve system test, further investigation of the presumed NPH patients with additional tests should be performed.

BACKGROUND: Idiopathic normal pressure hydrocephalus (INPH) is still a syndrome generating more questions than answers. Today, research focuses mainly on two areas: understanding the pathophysiology – especially how the malfunctioning CSF system affects the brain parenchyma – and finding better methods to select patients benefiting from a shunt operation. This thesis targets the aspect of finding better selection methods by investigating the measurability of intracranial pressure via lumbar space, and determining if intraparenchymal measurement of long-term ICP-oscillations (B-waves) could be replaced by short-term measurements of CSF pulse pressure waves via lumbar space. Furthermore, I look into the interaction between the CSF system and the parenchyma itself by investigating how the cortical activity of the brain changes after long-term CSF drainage, and if there is any regress in the suggested ischemia after this intervention. Finally, I examine if the neuronal integrity in the INPH brain is impaired, and if this feature is relevant for the likeliness of improvement after CSF diversion. METHODS: The comparison of intracranial and lumbar pressure was made over a vast pressure interval using our unique CSF infusion technique, and it included ten INPH patients. Pressure was measured via lumbar space and in brain tissue, and the pressures were compared using a general linear model. Short-term lumbar pressure waves were quantified by determining the slope between CSF pulse pressure and mean pressure, defined as the relative pulse pressure coefficient (RPPC). The correlation between RPPC, B-waves and CSF outflow resistance was investigated. In a prospective study, functional MRI was used to assess brain activity before and after long-term CSF drainage of 400 ml of CSF in eleven INPH patients. The functionalities tested included finger movement, memory, and attention. The results were benchmarked against the activity in ten healthy controls to identify the brain areas improving after drainage. The ischemia (Lactate) and neuronal integrity (NAA and Choline) were measured in a similar manner in 16 patients using proton MR spectroscopy, and the improvement of the patients after CSF drainage was based on assessment of their gait. RESULTS: There was excellent agreement between ICP measured in brain tissue and via lumbar space (regression coefficient = 0.98, absolute difference < 1 mm Hg). Adjusting for the separation distance between the measuring devices slightly worsened the agreement, indicating other factors influencing the measured difference as well. RPPC measured via lumbar space significantly correlated to the presence of B-waves, but not to outflow resistance. In the prospective study, controls outperformed patients on clinical tests as well as tasks related to the experiments. Improved behaviour after CSF drainage was found for motor function only, and it was accompanied by increased activation in the supplementary motor area (SMA). No lactate was detected, either before or after CSF drainage. NAA was decreased in INPH patients compared to controls, and the NAA levels were higher in the patients improving after drainage. CONCLUSIONS: ICP can be accurately measured via lumbar space in patients with communicating CSF systems. The close relation between RPPC and B-waves indicates that B-waves are primarily related to intracranial compliance, and that measurement of RPPC via lumbar space could possibly substitute B-wave assessment as selection method for finding suitable patients for shunt surgery. Improvement in motor function after CSF drainage was associated to enhanced activity in SMA, supporting the involvement of the cortico-basal ganglia-thalamo-cortical loop in the pathophysiology of INPH. There was no evidence indicating a widespread low-graded ischemia in INPH; however, there was a neuronal dysfunction in frontal white matter as indicated by the reduced levels of NAA. In addition, the level of neuronal dysfunction was related to the likeliness of improvement after CSF removal, normal levels of NAA predisposing for recovery.