Headache in patients with non-functioning pituitary adenoma before and after transsphenoidal surgery - a prospective study.

PURPOSE: To study the long-term effect of transsphenoidal surgery (TSS) on headache in patients with non-functioning pituitary adenoma (NFPA) and identify factors predicting headache relief following TSS. METHODS: We evaluated headache in 101 consecutive patients with NFPA who underwent TSS from September 2015 to December 2021, preoperatively and 12-months post-surgery, by using the Migraine Disability Assessment (MIDAS) questionnaire. Health-related quality of life (QoL) was assessed using the EQ-5D visual analogue scale (EQ-VAS). RESULTS: Of 101 patients, 27 (27%) experienced disabling preoperative headache. Among these, the median total MIDAS score improved from 60 (interquartile range (IQR): 19-140) to 10 (IQR: 0-49) (P = 0.004). Additionally, headache frequency over a 90-day period decreased from 45 (IQR: 25-83) to 6 (IQR: 3-36) days (P = 0.002), and headache intensity decreased from 5 (IQR: 4-7) to 4 (IQR: 2-7) (P = 0.016) at 12-months post-surgery. At 12 months post-surgery, 18 (67%) of 27 patients with preoperatively disabling headache showed clinically relevant improvement of their headache, 4 (15%) showed deterioration, and 5 (19%) remained unchanged. In patients with clinically relevant improvement of their headache, the EQ-VAS score improved from 50 (IQR: 30 - 7) to 80 (IQR: 65-86) (P < 0.001). Of the 74 patients with no preoperative headache, 11 (15%) developed postoperative headache. We identified no clinical factors predicting postoperative headache relief. CONCLUSION: The study supports that clinically significant and long-lasting improvements of disabling headache and QoL can be achieved with TSS in a substantial number of patients with NFPA.

Evaluation of a Fully Automated Method for Ventricular Volume Segmentation Before and After Shunt Surgery in Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND: Determination of the ventricle size in idiopathic normal pressure hydrocephalus (iNPH) is essential for diagnosis and follow-up of shunt results. Fully automated segmentation methods are anticipated to optimize the accuracy and time efficiency of ventricular volume measurements. We evaluated the accuracy of preoperative and postoperative ventricular volume measurements in iNPH by a magnetic resonance imaging (MRI)-based licensed software for fully automated quantitative assessment. METHODS: Forty-eight patients diagnosed with iNPH were retrospectively analyzed. All patients received a ventriculoperitoneal shunt and had symptom grading and routine MRI preoperatively and 3-6 months postoperatively. Ventricular volumes, generated by fully automated T1-weighted imaging volume sequence segmentation, were compared with semiautomatic measurements and routine radiologic reports. The relation of postoperative ventricular size change to clinical response was evaluated. RESULTS: Fully automated segmentation was achieved in 95% of the MRIs, but showed various rates of 8 minor segmentation errors. The correlation between both segmentation methods was very strong (r >0.9) and the agreement very good using Bland-Altman analyses. The ventricular volumes differed significantly between semiautomated and fully automated segmentations and between preoperative and postoperative MRI. The fully automated method systematically overestimated the ventricles by a median 15 mL preoperatively and 14 mL postoperatively; hence, the magnitudes of volume changes were equivalent. Routine radiologic reports of ventricular size changes were inaccurate in 51% and lacked association with treatment response. Objectively measured ventricular volume changes correlated moderately with postoperative clinical improvement. CONCLUSIONS: A fully automated volumetric method permits reliable evaluation of preoperative ventriculomegaly and postoperative ventricular volume change in idiopathic normal pressure hydrocephalus.

Volumetric effect of shunt adjustments in normal pressure hydrocephalus: a randomized, double-blind trial.

OBJECTIVE: MRI volumetry could be used as an alternative to invasive tests of shunt function. In this study, the authors aimed to assess the difference in ventricular volume (VV) before and after surgery and at different performance levels (PLs) of the shunt. METHODS: This study was a randomized, double-blind trial with a crossover design. The study sample consisted of 36 patients (25 men, 11 women) with a median age of 76 years. All patients had idiopathic normal pressure hydrocephalus (iNPH) and received a Strata shunt at the regional hospital in Östersund, Sweden, with an initial PL of 1.5. Participants underwent MRI with volumetric sequences before surgery and four times postoperatively: at 1 month before randomization to either PL 1.0 (n = 15) or 2.5 (n = 17); at 2 months before crossover to PL 2.5 or 1.0; at 3 months before lowering the PL to 0.5; and finally, at 3 months and 1 day after surgery before resetting the PL to 1.5. VV was measured semiautomatically using quantitative MRI. Both the patient and the examiner of clinical tests and volumetry were blinded to the PL. RESULTS: VV changed significantly between the presurgical level (median 129 ml) and the different shunt settings, i.e., PL 1.0 (median 115 ml), 1.5 (median 120 ml), and 2.5 (median 128 ml; p < 0.001). A unidirectional change in VV was observed for all participants between PL 1.0 and PL 2.5 (median 12 ml, range 2.1-40.7 ml, p < 0.001). No significant change was noted in VV after 24 hours at PL 0.5. Eight participants had asymptomatic subdural effusions at PL 1.0. CONCLUSIONS: The consistent decrease in VV after shunt surgery and between PL 2.5 and 1.0 supports the idea that MRI volumetry could be a noninvasive method for evaluating shunt function in iNPH, preventing unnecessary shunt revisions. However, further studies on retest variability of VV as well as verification against advanced testing of shunt function are needed before a clinical implementation of this method can be performed. Clinical trial registration no.: NCT04599153 (ClinicalTrials.gov).

Association between ventricular CSF biomarkers and outcome after shunt surgery in idiopathic normal pressure hydrocephalus.

INTRODUCTION: The relationship between neurochemical changes and outcome after shunt surgery in idiopathic normal pressure hydrocephalus (iNPH), a treatable dementia and gait disorder, is unclear. We used baseline ventricular CSF to explore associations to outcome, after shunting, of biomarkers selected to reflect a range of pathophysiological processes. METHODS: In 119 consecutive patients with iNPH, the iNPH scale was used before and after shunt surgery to quantify outcome. Ventricular CSF was collected perioperatively and analyzed for biomarkers of astrogliosis, axonal, amyloid and tau pathology, and synaptic dysfunction: glial fibrillary acidic protein (GFAP), chitinase-3-like protein 1 (YKL40/CHI3L1), monocyte chemoattractant protein-1 (MCP-1) neurofilament light (NfL), amyloid beta 38 (Aß38), Aß40, Aß42, amyloid beta 42/40 ratio (Aß42/40), soluble amyloid precursor protein alfa (sAPPα), sAPPß, total tau (T-tau), phosphorylated tau (P-tau), growth-associated protein 43 (GAP43), and neurogranin. RESULTS: The neurogranin concentration was higher in improved (68%) compared to unimproved patients (median 365 ng/L (IQR 186-544) vs 330 (205-456); p = 0.046). A linear regression model controlled for age, sex and vascular risk factors including neurogranin, T-tau, and GFAP, resulted in adjusted R2 = 0.06, p = 0.047. The Aß42/40 ratio was bimodally distributed across all samples, as well as in the subgroups of improved and unimproved patients but did not contribute to outcome prediction. The preoperative MMSE score was lower within the low Aß ratio group (median 25, IQR 23-28) compared to the high subgroup (26, 24-29) (p = 0.028). The T-Tau x Aß40/42 ratio and P-tau x Aß40/42 ratio did not contribute to shunt response prediction. The prevalence of vascular risk factors did not affect shunt response. DISCUSSION: A higher preoperative ventricular CSF level of neurogranin, which is a postsynaptic marker, may signal a favorable postoperative outcome. Concentrations of a panel of ventricular CSF biomarkers explained only 6% of the variability in outcome. Evidence of amyloid or tau pathology did not affect the outcome.

Endoscopic versus open microsurgery for colloid cysts of the third ventricle.

PURPOSE: The surgical approach for colloid cysts of the third ventricle mainly consists of endoscopic or microscopic approach but few studies compare the neurologic outcomes and complications related to the different approaches. We retrospectively reviewed our results after resection of colloid cysts of the third ventricle using endoscopic surgery (ES) compared to open microsurgery (OS). METHODS: Fifty-one patients were included in the study of which 17 patients underwent ES. Colloid cyst size and Evans' index were evaluated on CT or MRI scans. Presenting symptoms, neurologic outcomes and complications were compared between the two groups and analysed using Fisher's exact test. Operative time and days of hospital stay were compared between the two groups, using independent sample t-test. The median follow-up time was 96 days and did not differ significantly between the groups. RESULTS: Shorter mean operative time (p = 0.04) and fewer days of hospital stay (p < 0.01) were found in the endoscopic group compared to the open microsurgical group. Presenting symptoms, neurological outcomes and postoperative complications were similar in the two groups. CONCLUSIONS: ES showed similar neurologic outcomes and complications compared to OS for colloid cysts of the third ventricle. ES showed significantly shorter operative times and hospital stays compared to OS.

Ventricular volume in relation to lumbar CSF levels of amyloid-ß 1-42, tau and phosphorylated tau in iNPH, is there a dilution effect?

BACKGROUND: Levels of the biomarkers amyloid-ß 1-42 (Aß42), tau and phosphorylated tau (p-tau) are decreased in the cerebrospinal fluid (CSF) of patients with idiopathic normal pressure hydrocephalus (iNPH). The mechanism behind this is unknown, but one potential explanation is dilution by excessive CSF volumes. The aim of this study was to investigate the presence of a dilution effect, by studying the relationship between ventricular volume (VV) and the levels of the CSF biomarkers. METHODS: In this cross-sectional observational study, preoperative magnetic resonance imaging (MRI) and lumbar CSF was acquired from 136 patients with a median age of 76 years, 89 men and 47 females, selected for surgical treatment for iNPH. The CSF volume of the lateral and third ventricles was segmented on MRI and related to preoperative concentrations of Aß42, tau and p-tau. RESULTS: In the total sample VV (Median 140.7 mL) correlated weakly (rs = - 0.17) with Aß42 (Median 534 pg/mL), but not with tau (Median 216 pg/mL) nor p-tau (Median 31 pg/mL). In a subgroup analysis, the correlation between VV and Aß42 was only present in the male group (rs = - 0.22, p = 0.038). Further, Aß42 correlated positively with tau (rs = 0.30, p = 0.004) and p-tau (rs = 0.26, p = 0.012) in males but not in females. CONCLUSIONS: The findings did not support a major dilution effect in iNPH, at least not in females. The only result in favor for dilution was a weak negative correlation between VV and Aß42 but not with the other lumbar CSF biomarkers. The different results between males and females suggest that future investigations of the CSF pattern in iNPH would gain from sex-based subgroup analysis.

Long-Term Outcomes and Complications from Endoscopic Versus Microscopic Transsphenoidal Surgery for Cushing's Disease: A 15-Year Single-Center Study.

BACKGROUND: Endoscopic endonasal surgery is the main transsphenoidal approach for pituitary surgery in many centers; however, few studies compare the endoscopic and microscopic surgical approaches with regard to long-term follow-up. This single-center study aimed to compare the 2 techniques over 15 years. METHODS: Medical records and magnetic resonance images from 40 patients with primary transsphenoidal surgery for Cushing's disease at Sahlgrenska University Hospital between 2003 and 2018 were reviewed. 14 patients who underwent microscopic surgery and 26 patients who underwent endoscopic surgery were included in this study. RESULTS: In the microscopic group, 12 of 14 patients achieved endocrine remission, compared to 19 of 26 patients in the endoscopic group (n. s.). Three patients in each group developed a late recurrence. Complications were seen in 5 patients in the microscopic group and in 8 patients in the endoscopic group (n. s.). No serious complications, such as carotid artery damage, cerebrovascular fluid leakage, epistaxis, or meningitis, occurred in any group. The postoperative hospital stay was shorter in the endoscopic than in the microscopic group. CONCLUSIONS: Endoscopic endonasal surgery for Cushing's disease showed no difference in remission, recurrence, and complication rates compared to the microscopic approach. The endoscopic group had a shorter postoperative hospital stay than the microscopic group, which in part may be due to the minimal invasiveness of the endoscopic approach.

Sinonasal Symptoms and Self-Reported Health before and after Endoscopic Pituitary Surgery-A Prospective Study.

Objectives Despite the limited invasiveness of endoscopic transsphenoidal surgery (ETSS), some degree of nasal structure destruction is unavoidable. Our objective was to evaluate sinonasal morbidity and self-reported health before and 6 months after ETSS for pituitary tumors, and to identify possible predictive factors for deterioration in sinonasal health. Design Prospective observational cohort study. Setting University tertiary referral hospital. Participants Totally 109 consecutive adult patients undergoing ETSS for pituitary tumors between 2015 and 2019. Main Outcome Measures Sinonasal symptoms and self-reported health before and 6 months after ETSS, assessed by the Sinonasal Outcome Test (SNOT-22) and the EQ-5D questionnaire. Predictive factors for postoperative deterioration in sinonasal symptoms. Results The overall SNOT-22 score did not change, but the score of the rhinologic domain of SNOT-22 worsened from 6.0 ± 5.9 before to 8.0 ± 7.4 6 months after surgery ( p = 0.011). The EQ-5D visual analog scale improved from 64.0 ± 22.9 before to 71.1 ± 18.7 6 months after surgery ( p = 0.00088). Univariate and multivariable regression analyses showed that prior sinonasal surgery was associated with a significant worsening in rhinologic symptoms 6 months after surgery ( p = 0.046 and p = 0.020, respectively). Conclusions Although self-reported overall health improved, significant deterioration of rhinologic symptoms was seen 6 months after ETSS. This information is important for preoperative patient counselling. Further refinement of the surgical technique and follow-up strategies to reduce postoperative sinonasal morbidity could be of value, especially in patients who have undergone prior sinonasal surgery.

Headache Before and After Endoscopic Transsphenoidal Pituitary Tumor Surgery: A Prospective Study.

Objective Headache is a common symptom among patients with pituitary tumors, as it is in the general population. The aim of the study was to investigate headache as a symptom in patients with pituitary tumors before and 6 months after endoscopic transsphenoidal surgery (TSS). Design This is a prospective observational cohort study. Setting This study was conducted at university tertiary referral hospital. Participants A total of 110 adult patients underwent endoscopic TSS for pituitary tumors. Main Outcome Measures The Migraine Disability Assessment (MIDAS) questionnaire was used before and 6 months after surgery for the assessment of headache. Clinical variables with potential influence on headache were analyzed. Results Sixty-eight (62%) patients experienced headaches at least once during the 3 months before surgery. Thirty (27%) patients reported disabling headache before surgery, with younger age being an independent associated factor ( p < 0.001). In patients with disabling headache before surgery, the median (interquartile range) MIDAS score improved from 78 (27-168) to 16 (2-145; p = 0.049), headache frequency decreased from 45 (20-81) to 14 (4-35) days ( p = 0.009), and headache intensity decreased from 6 (5-8) to 5 (4-7) ( p = 0.011) after surgery. In total, 16 of the 30 (53%) patients reported a clinically relevant improvement and five (17%) a clinically relevant worsening. Four (5%) patients developed new disabling headache. No predictor for postoperative improvement of headache was identified. Conclusion In this prospective study, the results show that disabling headache improves following endoscopic TSS in a subset of patients with pituitary tumors. However, no predictive factors for improvement could be identified.

Circulating brain injury biomarkers increase after endoscopic surgery for pituitary tumors.

Pituitary tumors and subsequent treatment with endoscopic transsphenoidal surgery (ETSS) may cause injury to suprasellar structures, causing long-term fatigue and neurocognitive impairment. A method to quantify brain injury after ETSS is not available. In this prospective, exploratory study of patients undergoing ETSS for pituitary tumors, a novel approach to detect possible neuronal damage is presented. Plasma concentrations of brain injury biomarkers (glial fibrillary acidic protein [GFAP], tau, and neurofilament light [NFL]) were measured the day before surgery, immediately after surgery, at day 1 and 5, and at 6 and 12 months after surgery, using enzyme-linked immunosorbent assays. The association between the increase of biomarkers with preoperative tumor extension and postoperative patient-perceived fatigue was evaluated. Suprasellar tumor extension was assessed from MRI scans, and self-perceived fatigue was assessed using the Multidimensional Fatigue Inventory before and 6 months after surgery. Thirty-five patients were included in the analysis. Compared to baseline, GFAP showed a maximal increase at day 1 after surgery (p = 0.0005), tau peaked postoperatively on the day of surgery (p = 0.019), and NFL reached its maximum at day 5 after surgery (p < 0.0001). The increase in GFAP correlated with preoperative chiasmal compression (p = 0.020). The increase in tau was correlated with preoperative chiasmal (p = 0.011) and hypothalamus compression (p = 0.016), and fatigue score 6 months after surgery (p = 0.016). In conclusion, the concentrations of brain injury biomarkers in blood increased after ETSS for pituitary tumors. The results indicate that postoperative plasma GFAP and tau might reflect astroglial and neuronal damage after ETSS.

Virtual magnetic resonance elastography has the feasibility to evaluate preoperative pituitary adenoma consistency.

PURPOSE: To evaluate the use of preoperative virtual Magnetic Resonance Elastography (vMRE) for patients undergoing transsphenoidal resection of pituitary adenomas (PA). METHODS: Ten patients (60.2 ± 19.6 years; 8 males) were prospectively examined with the vMRE-method prior to transsphenoidal surgery. vMRE-images, reflecting tissue stiffness were reconstructed. From these images, histograms as well as the mean stiffness values over the tumor body were extracted. Finally, vMRE-data was compared with the PA consistency at surgery blinded to vMRE. RESULTS: In all patients, successful vMRE-examination was performed enabling evaluation of even small PAs. For tumors with homogenous tissue, the mean stiffness value increased with surgical consistency grading. For heterogenous tumors, however, the mean stiffness value did not consistently reflect the grading at surgery. On the other hand, the vMRE-images and histograms were found to be able to characterize the tumor heterogeneity and display focal regions of high stiffness that were found to affect the surgery outcome in these PAs. The vMRE-images and histograms showed great promise in characterizing the consistency at surgery for these PAs. CONCLUSION: Evaluation of PA consistency in preparation for surgery seems to be feasible using the vMRE-method. Our findings also address the need for high resolution diagnostic methods that can non-invasively display focal regions of increased stiffness, as such regions may increase the difficulty of transsphenoidal PA-resection.

Indications and outcome in surgically treated asymptomatic meningiomas: a single-center case-control study.

BACKGROUND: Many meningiomas are detected incidentally and remain asymptomatic until intervention. The goal of this study was to describe the management and outcome in this group of surgically treated asymptomatic meningiomas. METHODS: From 2004 to 2017, 45 patients with asymptomatic meningioma were surgically treated at Sahlgrenska University Hospital, and their medical records and imaging data were analyzed. The asymptomatic cases were matched with symptomatic ones with respect to age at diagnosis, location, WHO (World Health Organization) grade, and Simpson grade. RESULTS: Time from diagnosis to surgery differed between the asymptomatic and symptomatic patients (8.6 vs. 1.3 months; p < 0.001). Of symptomatic patients, 32.6% still used anti-epileptic drugs > 1 year after surgery, compared with 7.7% of the asymptomatic (p = 0.003). Thirty-day complication rate was significantly higher among the asymptomatic cases (35.6% vs. 24.4%; 0.001), as well as the proportion of older asymptomatic individuals (> 70 years) experiencing postoperative complication compared with symptomatic patients of the same age group. CONCLUSION: As expected, asymptomatic cases had smaller tumors and waited longer for surgery. Surprisingly, complication rate was significantly higher among asymptomatic cases compared with their symptomatic control. Taken into account that many asymptomatic tumors are removed surgically due to patient's wish, one might suggest a more restrictive approach, especially in the elderly.

Intracranial Manifestation of Melioidosis: A Case Report and Long-Term Follow-Up.

Primary neurological melioidosis is rare with fewer than 50 cases reported world-wide. We report the first documented case of primary neurological melioidosis in Sweden, a 32-year old male who previously lived in Thailand for six years and recently moved to Sweden. He presented with headache, irritability and lack of concentration. Investigation with computerized tomography (CT) and subsequent magnetic resonance imaging (MRI) showed epidural fluid that was interpreted as a chronic epidural hematoma. He underwent surgical evacuation of the epidural collection that was found to be a white collection mixed with pus and bacterial culture results were positive for Burkholderia pseudomallei.

Neurosurgical treatment and outcome patterns of meningioma in Sweden: a nationwide registry-based study.

BACKGROUND: Surgery is the main treatment modality for intracranial meningiomas, but data on short-term surgical outcome are limited. The aim of this Swedish nationwide registry-based study was to benchmark the 30-day complication rate in a cohort of meningioma patients using data from the Swedish brain tumor registry (SBTR). Furthermore, we investigated outcomes for asymptomatic patients. METHODS: Data were collected from the SBTR for all adults with histopathologically verified intracranial meningioma between 2009 and 2015. Patient symptoms, tumor characteristics, and complications within 30 days postoperatively were analyzed. RESULTS: In total, 2324 patients, with a mean age of 58.7 years (SD 13.5), underwent surgery for intracranial meningioma and 14.1% of the patients were asymptomatic before the intervention. The most common symptom prior to treatment was focal deficit, which occurred in 1450 patients (62.4%). Moreover, within 30 days after surgery, 344 patients (14.8%) developed new neurological deficits and new-onset seizures occurred in 105 patients (4.5%), while 8.3% of asymptomatic patients developed neurological deficit and 3.7% new-onset seizures. Due to complications, reoperations were performed in 120 patients (5.2%). The postoperative 30-day mortality in the whole cohort was 1.5%. CONCLUSION: This study benchmarks the 30-day complication rate after meningioma surgery and provides outcome data in the highly relevant group of asymptomatic patients using data from the Swedish brain tumor registry. Since surgical decision-making is a careful consideration of short-term risk versus long-term benefit, this information may be useful for both caregivers and patients.

Three-Dimensional Volumetric Segmentation of Pituitary Tumors: Assessment of Inter-rater Agreement and Comparison with Conventional Geometric Equations.

Background The assessment of pituitary tumor (PT) volume is important in the treatment and follow-up of patients with PT. Previously, PT volume estimation has been performed by conventional geometric equations (CGE) such as abc/2 (simplified ellipsoid volume equation) and 4πr 3 /3 (sphere), both presuming a symmetric tumor shape, which occurs uncommonly in patients with PT. In contrast, three-dimensional (3D) voxel-based software segmentation takes the irregular and asymmetric shapes that PTs often possess into account and might be a more accurate method for PT volume segmentation. The purpose of this study is twofold. (1) To compare 3D segmentation with CGE for PT volume estimation. (2) To assess inter-rater reliability in 3D segmentation of PTs. Methods Nineteen high-resolution (1mm slice thickness) T1-weighted MRI examinations of patients with PT were independently analyzed and manually segmented, using the software ITK-SNAP, by two certified neuroradiologists. Concurrently, the volumes of the PTs were estimated with abc/2 and 4πr 3 /3 by a clinician, and the results were compared with the corresponding segmented volumes. Results There was a significant decrease in PT volume attained from the segmentations compared with the calculations made with abc/2 ( p < 0.001, mean volume 18% higher than segmentation) and 4πr 3 /3 ( p < 0.001, mean volume 28% higher than segmentation). The intraclass correlation coefficient (ICC) for the two sets of segmented PTs was 0.99. Conclusion CGE ( abc/2 and 4πr 3 /3 ) significantly overestimates PT volume compared with 3D volumetric segmentation. The inter-rater agreement on manual 3D volumetric software segmentation is excellent.

Determinants for Effective ALECSAT Immunotherapy Treatment on Autologous Patient-Derived Glioblastoma Stem Cells.

Glioblastoma (GBM) is the most aggressive primary brain tumor with a median survival of less than 15 months, emphasizing the need for better treatments. Immunotherapy as a treatment for improving or aiding the patient's own immune defense to target the tumor has been suggested for GBM. A randomized clinical trial of adoptive cell transfer using ALECSAT (Autologous Lymphoid Effector Cells Specific Against Tumor Cells) is currently ongoing in Sweden. Here we performed a paired pre-clinical study to investigate the composition and in vitro effect of ALECSAT and identify determinants for the effect using autologous GBM-derived cancer stem cells (CSC), immunocytochemistry and flow cytometry. We show a clear dose-response relationship of ALECSAT on CSC, suggesting that the number of infused cells is of importance. In addition, the in vitro effect of ALECSAT on CSC correlated significantly to the blood count of T helper (Th) cells in the patient indicating a potential benefit of collecting cells for ALECSAT preparation at an even earlier stage when patients generally have a better blood count. The factors identified in this study will be important to consider in the design of future immunotherapy trials to achieve prolonged survival.

A double-blind randomized trial on the clinical effect of different shunt valve settings in idiopathic normal pressure hydrocephalus.

OBJECTIVE: The study aim was to examine the effect of gradually reducing the opening pressure on symptoms and signs in the shunt treatment of idiopathic normal pressure hydrocephalus (iNPH). METHODS: In this prospective double-blinded, randomized, controlled, double-center study on patients with iNPH, a ventriculoperitoneal shunt with an adjustable Codman Medos Valve was implanted in 68 patients randomized into 2 groups. In 1 group (the 20-4 group) the valve setting was initially set to 20 cm H2O and gradually reduced to 4 cm H2O over the course of the 6-month study period. In the other group (the 12 group), the valve was kept at a medium level of 12 cm H2O during the whole study period. All patients were clinically evaluated using 4 tests preoperatively as well as postoperatively at 1, 2, 3, 4, and 6 months. The test scores between the 2 groups (20-4 and 12) were compared for each clinical evaluation. RESULTS: Fifty-five patients (81%) were able to complete the study. There were no significant differences between the 2 groups (20-4 and 12) preoperatively or at any time postoperatively. Both groups exhibited significant clinical improvement after shunt insertion at all valve settings compared with the preoperative score, with the greatest improvement observed at the first postoperative evaluation. The clinical improvement was significant within the first 3 months, and thereafter no significant improvement was seen in either group. CONCLUSIONS: Gradual reduction of the valve setting from 20 to 4 cm H2O did not improve outcome compared with a fixed valve setting of 12 cm H2O. Improvement after shunt surgery in iNPH patients was evident within 3 months, irrespective of valve setting.

Intracranial pressure in hydrocephalus: impact of shunt adjustments and body positions.

BACKGROUND: The association between intracranial pressure (ICP) and different shunt valve opening pressures in relation to body positions is fundamental for understanding the physiological function of the shunt. OBJECTIVE: To analyse the ICP and ICP wave amplitude (AMP) at different shunt settings and body positions in patients with hydrocephalus. METHODS: In this prospective study 15 patients with communicating hydrocephalus were implanted with a ligated adjustable ventriculoperitoneal shunt. They also received a portable intraparenchymatous ICP-monitoring device. Postoperative ICP and AMP were recorded with the patients in three different body positions (supine, sitting and walking) and with the shunt ligated and open at high, medium and low valve settings. In each patient 12 10 min segments were coded, blinded and analysed for mean ICP and mean AMP using an automated computer algorithm. RESULTS: Mean ICP and mean AMP were lower at all three valve settings compared with the ligated shunt state (p<0.001). Overall, when compared with the supine position, mean ICP was 11.5±1.1 (mean±SD) mm Hg lower when sitting and 10.5±1.1 mm Hg lower when walking (p<0.001). Mean ICP was overall 1.1 mm Hg higher (p=0.042) when walking compared with sitting. The maximal adjustability difference (highest vs lowest valve setting) was 4.4 mm Hg. CONCLUSIONS: Changing from a supine to an upright position reduced ICP while AMP only increased at trend level. Lowering of the shunt valve opening pressure decreased ICP and AMP but the difference in mean ICP in vivo between the highest and lowest opening pressures was less than half that previously observed in vitro.

A randomized controlled dual-center trial on shunt complications in idiopathic normal-pressure hydrocephalus treated with gradually reduced or "fixed" pressure valve settings.

OBJECT: This study was undertaken to investigate whether a gradual reduction of the valve setting (opening pressure) decreases the complication rate in patients with idiopathic normal-pressure hydrocephalus (iNPH) treated with a ventriculoperitoneal (VP) shunt. METHODS: In this prospective double-blinded, randomized, controlled, dual-center study, a VP shunt with an adjustable valve was implanted in 68 patients with iNPH, randomized into two groups. In one group (the 20-4 group) the valve setting was initially set to 20 cm H2O and gradually reduced to 4 cm H2O over the course of the 6-month study period. In the other group (the 12 group), the valve was kept at a medium pressure setting of 12 cm H2O during the whole study period. The time to and type of complications (hematoma, infection, and mechanical problems) as well as overdrainage symptoms were recorded. Symptoms, signs, and outcome were assessed by means of the iNPH scale and the NPH grading scale. RESULTS: Six patients in the 20-4 group (22%) and 7 patients in the 12 group (23%) experienced a shunt complication; 9 had subdural hematomas, 3 mechanical obstructions, and 1 infection (no significant difference between groups). The frequency of overdrainage symptoms was significantly higher for a valve setting ≤ 12 cm H2O compared with a setting > 12 cm H2O. The 20-4 group had a higher improvement rate (88%) than the 12 group (62%) (p = 0.032). There was no significant relationship between complications and body mass index, the use of an antisiphon device, or the use of anticoagulants. CONCLUSIONS: Gradual lowering of the valve setting to a mean of 7 cm H2O led to the same rate of shunt complications and overdrainage symptoms as a fixed valve setting at a mean of 13 cm H2O but was associated with a significantly better outcome.