A multitrait genetic study of hemostatic factors and hemorrhagic transformation after stroke treatment.

BACKGROUND: Thrombolytic recombinant tissue plasminogen activator (r-tPA) treatment is the only pharmacologic intervention available in the ischemic stroke acute phase. This treatment is associated with an increased risk of intracerebral hemorrhages, known as hemorrhagic transformations (HTs), which worsen the patient's prognosis. OBJECTIVES: To investigate the association between genetically determined natural hemostatic factors' levels and increased risk of HT after r-tPA treatment. METHODS: Using data from genome-wide association studies on the risk of HT after r-tPA treatment and data on 7 hemostatic factors (factor [F]VII, FVIII, von Willebrand factor [VWF], FXI, fibrinogen, plasminogen activator inhibitor-1, and tissue plasminogen activator), we performed local and global genetic correlation estimation multitrait analyses and colocalization and 2-sample Mendelian randomization analyses between hemostatic factors and HT. RESULTS: Local correlations identified a genomic region on chromosome 16 with shared covariance: fibrinogen-HT, P = 2.45 × 10-11. Multitrait analysis between fibrinogen-HT revealed 3 loci that simultaneously regulate circulating levels of fibrinogen and risk of HT: rs56026866 (PLXND1), P = 8.80 × 10-10; rs1421067 (CHD9), P = 1.81 × 10-14; and rs34780449, near ROBO1 gene, P = 1.64 × 10-8. Multitrait analysis between VWF-HT showed a novel common association regulating VWF and risk of HT after r-tPA at rs10942300 (ZNF366), P = 1.81 × 10-14. Mendelian randomization analysis did not find significant causal associations, although a nominal association was observed for FXI-HT (inverse-variance weighted estimate [SE], 0.07 [-0.29 to 0.00]; odds ratio, 0.87; 95% CI, 0.75-1.00; raw P = .05). CONCLUSION: We identified 4 shared loci between hemostatic factors and HT after r-tPA treatment, suggesting common regulatory mechanisms between fibrinogen and VWF levels and HT. Further research to determine a possible mediating effect of fibrinogen on HT risk is needed.

Early and Delayed Infarct Growth in Patients Undergoing Mechanical Thrombectomy: A Prospective, Serial MRI Study.

BACKGROUND: We studied the evolution over time of diffusion weighted imaging (DWI) lesion volume and the factors involved on early and late infarct growth (EIG and LIG) in stroke patients undergoing endovascular treatment (EVT) according to the final revascularization grade. METHODS: This is a prospective cohort of patients with anterior large artery occlusion undergoing EVT arriving at 1 comprehensive stroke center. Magnetic resonance imaging was performed on arrival (pre-EVT), <2 hours after EVT (post-EVT), and on day 5. DWI lesions and perfusion maps were evaluated. Arterial revascularization was assessed according to the modified Thrombolysis in Cerebral Infarction (mTICI) grades. We recorded National Institutes of Health Stroke Scale at arrival and at day 7. EIG was defined as (DWI volume post-EVT-DWI volume pre-EVT), and LIG was defined as (DWI volume at 5d-DWI volume post-EVT). Factors involved in EIG and LIG were tested via multivariable lineal models. RESULTS: We included 98 patients (mean age 70, median National Institutes of Health Stroke Scale score 17, final mTICI≥2b 86%). Median EIG and LIG were 48 and 63.3 mL in patients with final mTICI<2b, and 3.6 and 3.9 cc in patients with final mTICI≥2b. Both EIG and LIG were associated with higher National Institutes of Health Stroke Scale at day 7 (ρ=0.667; P<0.01 and ρ=0.614; P<0.01, respectively). In patients with final mTICI≥2b, each 10% increase in the volume of DWI pre-EVT and each extra pass leaded to growths of 9% (95% CI, 7%-10%) and 14% (95% CI, 2%-28%) in the DWI volume post-EVT, respectively. Furthermore, each 10% increase in the volume of DWI post-EVT, each extra pass, and each 10 mL increase in TMax6s post-EVT were associated with growths of 8% (95% CI, 6%-9%), 9% (95% CI, 0%-19%), and 12% (95% CI, 5%-20%) in the volume of DWI post-EVT, respectively. CONCLUSIONS: Infarct grows during and after EVT, especially in nonrecanalizers but also to a lesser extent in recanalizers. In recanalizers, number of passes and DWI volume influence EIG, while number of passes, DWI, and hypoperfused volume after the procedure determine LIG.

A Polygenic Risk Score Based on a Cardioembolic Stroke Multitrait Analysis Improves a Clinical Prediction Model for This Stroke Subtype.

Background: Occult atrial fibrillation (AF) is one of the major causes of embolic stroke of undetermined source (ESUS). Knowing the underlying etiology of an ESUS will reduce stroke recurrence and/or unnecessary use of anticoagulants. Understanding cardioembolic strokes (CES), whose main cause is AF, will provide tools to select patients who would benefit from anticoagulants among those with ESUS or AF. We aimed to discover novel loci associated with CES and create a polygenetic risk score (PRS) for a more efficient CES risk stratification. Methods: Multitrait analysis of GWAS (MTAG) was performed with MEGASTROKE-CES cohort (n = 362,661) and AF cohort (n = 1,030,836). We considered significant variants and replicated those variants with MTAG p-value < 5 × 10-8 influencing both traits (GWAS-pairwise) with a p-value < 0.05 in the original GWAS and in an independent cohort (n = 9,105). The PRS was created with PRSice-2 and evaluated in the independent cohort. Results: We found and replicated eleven loci associated with CES. Eight were novel loci. Seven of them had been previously associated with AF, namely, CAV1, ESR2, GORAB, IGF1R, NEURL1, WIPF1, and ZEB2. KIAA1755 locus had never been associated with CES/AF, leading its index variant to a missense change (R1045W). The PRS generated has been significantly associated with CES improving discrimination and patient reclassification of a model with age, sex, and hypertension. Conclusion: The loci found significantly associated with CES in the MTAG, together with the creation of a PRS that improves the predictive clinical models of CES, might help guide future clinical trials of anticoagulant therapy in patients with ESUS or AF.

RP11-362K2.2:RP11-767I20.1 Genetic Variation Is Associated with Post-Reperfusion Therapy Parenchymal Hematoma. A GWAS Meta-Analysis.

Stroke is one of the most common causes of death and disability. Reperfusion therapies are the only treatment available during the acute phase of stroke. Due to recent clinical trials, these therapies may increase their frequency of use by extending the time-window administration, which may lead to an increase in complications such as hemorrhagic transformation, with parenchymal hematoma (PH) being the more severe subtype, associated with higher mortality and disability rates. Our aim was to find genetic risk factors associated with PH, as that could provide molecular targets/pathways for their prevention/treatment and study its genetic correlations to find traits sharing genetic background. We performed a GWAS and meta-analysis, following standard quality controls and association analysis (fastGWAS), adjusting age, NIHSS, and principal components. FUMA was used to annotate, prioritize, visualize, and interpret the meta-analysis results. The total number of patients in the meta-analysis was 2034 (216 cases and 1818 controls). We found rs79770152 having a genome-wide significant association (beta 0.09, p-value 3.90 × 10-8) located in the RP11-362K2.2:RP11-767I20.1 gene and a suggestive variant (rs13297983: beta 0.07, p-value 6.10 × 10-8) located in PCSK5 associated with PH occurrence. The genetic correlation showed a shared genetic background of PH with Alzheimer's disease and white matter hyperintensities. In addition, genes containing the ten most significant associations have been related to aggregated amyloid-ß, tau protein, white matter microstructure, inflammation, and matrix metalloproteinases.

Cerebrospinal Fluid Output as a Risk Factor of Chronic Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Chronic shunt-dependent hydrocephalus is a well-known complication of subarachnoid hemorrhage. Although the risk factors have been extensively investigated, most fail to predict permanent shunt dependency. It is unknown whether the volume of cerebrospinal fluid (CSF) from external ventricular drainage and the daily volume of drainage during the acute hydrocephalus phase (first 72 hours) can predict shunt dependency. We aimed to determine whether CSF output during the acute hydrocephalus phase is a risk factor for shunt dependency. METHODS: Patients with aneurysmal subarachnoid hemorrhage and hydrocephalus treated with external ventricular drainage were prospectively registered in our database between January 2017 and March 2020. Factors evaluated for predicting shunt dependency included age; sex; Hunt and Hess grade; World Federation of Neurological Surgeons grade; acute hydrocephalus; modified Fisher grade; aneurysm treatment modality; hospital length of stay; modified Rankin score; average daily overall CSF production; average CSF output for the first 24, 48, and 72 hours; external ventricular drainage days; the number of wean/clamp failures; and ventriculoperitoneal shunting. RESULTS: Univariate analysis identified Hunt and Hess grade; acute hydrocephalus at onset; external ventricular drainage; overall CSF output; average CSF output for the first 24, 48, and 72 hours; and CSF output until the first clamp as significant risk factors for shunt dependency (P < 0.001). In a multivariate logistic regression analysis, overall CSF output and average CSF output for the first 72 hours were significant risk factors for shunt dependency. CONCLUSIONS: Overall CSF output, especially during the acute hydrocephalus phase (first 72 hours), predicts the development of chronic hydrocephalus.

Single nucleotide variations in ZBTB46 are associated with post-thrombolytic parenchymal haematoma.

Haemorrhagic transformation is a complication of recombinant tissue-plasminogen activator treatment. The most severe form, parenchymal haematoma, can result in neurological deterioration, disability, and death. Our objective was to identify single nucleotide variations associated with a risk of parenchymal haematoma following thrombolytic therapy in patients with acute ischaemic stroke. A fixed-effect genome-wide meta-analysis was performed combining two-stage genome-wide association studies (n = 1904). The discovery stage (three cohorts) comprised 1324 ischaemic stroke individuals, 5.4% of whom had a parenchymal haematoma. Genetic variants yielding a P-value < 0.05 1 × 10-5 were analysed in the validation stage (six cohorts), formed by 580 ischaemic stroke patients with 12.1% haemorrhagic events. All participants received recombinant tissue-plasminogen activator; cases were parenchymal haematoma type 1 or 2 as defined by the European Cooperative Acute Stroke Study (ECASS) criteria. Genome-wide significant findings (P < 5 × 10-8) were characterized by in silico functional annotation, gene expression, and DNA regulatory elements. We analysed 7 989 272 single nucleotide polymorphisms and identified a genome-wide association locus on chromosome 20 in the discovery cohort; functional annotation indicated that the ZBTB46 gene was driving the association for chromosome 20. The top single nucleotide polymorphism was rs76484331 in the ZBTB46 gene [P = 2.49 × 10-8; odds ratio (OR): 11.21; 95% confidence interval (CI): 4.82-26.55]. In the replication cohort (n = 580), the rs76484331 polymorphism was associated with parenchymal haematoma (P = 0.01), and the overall association after meta-analysis increased (P = 1.61 × 10-8; OR: 5.84; 95% CI: 3.16-10.76). ZBTB46 codes the zinc finger and BTB domain-containing protein 46 that acts as a transcription factor. In silico studies indicated that ZBTB46 is expressed in brain tissue by neurons and endothelial cells. Moreover, rs76484331 interacts with the promoter sites located at 20q13. In conclusion, we identified single nucleotide variants in the ZBTB46 gene associated with a higher risk of parenchymal haematoma following recombinant tissue-plasminogen activator treatment.

Early Neurological Change After Ischemic Stroke Is Associated With 90-Day Outcome.

BACKGROUND AND PURPOSE: Large-scale observational studies of acute ischemic stroke (AIS) promise to reveal mechanisms underlying cerebral ischemia. However, meaningful quantitative phenotypes attainable in large patient populations are needed. We characterize a dynamic metric of AIS instability, defined by change in National Institutes of Health Stroke Scale score (NIHSS) from baseline to 24 hours baseline to 24 hours (NIHSSbaseline - NIHSS24hours = ΔNIHSS6-24h), to examine its relevance to AIS mechanisms and long-term outcomes. METHODS: Patients with NIHSS prospectively recorded within 6 hours after onset and then 24 hours later were enrolled in the GENISIS study (Genetics of Early Neurological Instability After Ischemic Stroke). Stepwise linear regression determined variables that independently influenced ΔNIHSS6-24h. In a subcohort of tPA (alteplase)-treated patients with large vessel occlusion, the influence of early sustained recanalization and hemorrhagic transformation on ΔNIHSS6-24h was examined. Finally, the association of ΔNIHSS6-24h with 90-day favorable outcomes (modified Rankin Scale score 0-2) was assessed. Independent analysis was performed using data from the 2 NINDS-tPA stroke trials (National Institute of Neurological Disorders and Stroke rt-PA). RESULTS: For 2555 patients with AIS, median baseline NIHSS was 9 (interquartile range, 4-16), and median ΔNIHSS6-24h was 2 (interquartile range, 0-5). In a multivariable model, baseline NIHSS, tPA-treatment, age, glucose, site, and systolic blood pressure independently predicted ΔNIHSS6-24h (R2=0.15). In the large vessel occlusion subcohort, early sustained recanalization and hemorrhagic transformation increased the explained variance (R2=0.27), but much of the variance remained unexplained. ΔNIHSS6-24h had a significant and independent association with 90-day favorable outcome. For the subjects in the 2 NINDS-tPA trials, ΔNIHSS3-24h was similarly associated with 90-day outcomes. CONCLUSIONS: The dynamic phenotype, ΔNIHSS6-24h, captures both explained and unexplained mechanisms involved in AIS and is significantly and independently associated with long-term outcomes. Thus, ΔNIHSS6-24h promises to be an easily obtainable and meaningful quantitative phenotype for large-scale genomic studies of AIS.

Coping Strategies, Quality of Life, and Neurological Outcome in Patients Treated with Mechanical Thrombectomy after an Acute Ischemic Stroke.

New reperfusion therapies have improved the clinical recovery rates of acute ischemic stroke patients (AISP), but it is not known whether other factors, such as the ability to cope, might also have an effect. The aim of this study was to evaluate the effect of endovascular treatment (EVT) on coping strategies, quality of life, and neurological and functional outcomes in AISP at 3 months and 1 year post-stroke. A multicenter, prospective, longitudinal, and comparative study of a sub-study of the participants in the Endovascular Revascularization with Solitaire Device versus Best Medical Therapy in Anterior Circulation Stroke within 8 Hours (REVASCAT) clinical trial was conducted after recruiting from two stroke centers in Catalonia, Spain. The cohort consisted of 82 ischemic stroke patients (n = 42 undergoing EVT and n = 40 undergoing standard best medical treatment (BMT) as a control group), enrolled between 2013-2015. We assessed the coping strategies using the Brief Coping Questionnaire (Brief-COPE-28), the health-related quality of life (HRQoL) with the EQ-5D questionnaire, and the neurological and functional status using the National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), modified Rankin Scale (mRS), and Stroke Impact Scale-16 (SIS-16). Bivariate analyses and multivariate linear regression models were used. EVT patients were the ones that showed better neurological and functional outcomes, and more patients presented reporting no pain/discomfort at 3 months; paradoxically, problem-focused coping strategies were found to be significantly higher in patients treated with BMT at 1 year.

E-Learning course for nurses on pain assessment in patients unable to self-report.

Public hospitals in Catalonia, Spain, have recommended assessing pain in non-communicative inpatients by means of the Spanish version of the Pain Assessment in Advanced Dementia scale (PAINAD-Sp) since 2010; a modification for patients with neurologic disorders and cancer, PAINAD-Sp_Hosp, has also been validated. However, nurses are not routinely trained in the use of the scales. The aim of this study was to assess knowledge on pain assessment in nurses following an online training course. We surveyed participants prior to the course to determine baseline knowledge of pain and pain assessment. Course material included conceptual content on pain and practical videos demonstrating the scoring system for the PAINAD-Sp_Hosp scale. After completing the course, participants took a multiple choice quiz to test understanding of course content and a satisfaction survey to determine acceptability. Of the 836 nurses invited, 401 participated in the training course; 37.7% reported having no previous specific training on pain, and just 32.2% used the PAINAD-Sp scale regularly. Following the course, virtually all (99%) of the participants passed the quiz. Overall satisfaction among nurses with regard to the training received was 8.6/10. Thus, the e-learning course was effective and acceptable for training nurses on pain assessment using validated tools.

Stroke Risk Analysis, a System With a High Detection Rate of Atrial Fibrillation in Stroke and Transient Ischemic Attack.

Background and Purpose- Stroke Risk Analysis (SRA) comprises an algorithm for automated analysis of ECG monitoring, enabling the detection of paroxysmal atrial fibrillation (pxAF) and identifying patterns indicating a high risk of atrial fibrillation (R_AF). We compared Holter-enabled continuous ECG monitoring in combination with SRA (hSRA) with standard continuous ECG monitoring for pxAF detection in patients with acute ischemic stroke. Also, we sought to identify whether the detection of R_AF patterns during the first cycle (first 2 hours) of hSRA recording was associated with the detection of pxAF during the Stroke Unit stay. Methods- We enrolled 524 consecutive patients admitted in the Stroke Unit with acute ischemic stroke or transient ischemic attack with neither history of AF nor AF at admission into a prospective multicentric observational analytic clinical study with intrapatient comparison, who received both continuous ECG monitoring as well as hSRA up to 7 days. Investigators were blinded to hSRA results unless pxAF was detected on SRA. Results- Of the 524 consecutive acute stroke patients (median age, 70.0 years; 60% male; acute ischemic stroke 93%, transient ischemic attack 7%), 462 were eligible and included in the study. Among 462 patients with hSRA available for 66 hours, AF was documented by hSRA in 79 patients (17.1%). From this group, 45 AF cases (9.7%) were confirmed after review by an independent and blinded cardiologist. continuous ECG monitoring detected 21 AF cases (4.3%; P<0.0001). hSRA detected R_AF patterns in 92 patients. 35 out of the 92 R_AF patients showed an episode of AF during the Stroke Unit stay. Predictive values of R_AF patterns within the first cycle of hSRA were: sensitivity 71%, specificity 86%, positive predictive value 38%, and negative predictive value 96%. Conclusions- Automated analysis using SRA technology strongly improves pxAF detection in acute ischemic stroke patients compared with continuous ECG monitoring. The predictive value of a R_AF pattern, as detected by hSRA during the first few hours after admission, deserves further investigation.

Genome-Wide Association Study of White Blood Cell Counts in Patients With Ischemic Stroke.

Background and Purpose- Immune cells play a key role in the first 24h poststroke (acute phase), being associated with stroke outcome. We aimed to find genetic risk factors associated with leukocyte counts during the acute phase of stroke. Methods- Ischemic stroke patients with leukocyte counts data during the first 24h were included. Genome-wide association study and gene expression studies were performed. Results- Our genome-wide association study, which included 2064 (Discovery) and 407 (Replication) patients, revealed a new locus (14q24.3) associated with leukocyte counts. After Joint analysis (n=2471) 5 more polymorphisms reached genome-wide significance (P<5×10-8). The 14q24.3 locus was associated with acute stroke outcome (rs112809786, P=0.036) and with ACOT1 and PTGR2 gene expression. Previous polymorphisms associated with leukocyte counts in general-population did not show any significance in our study. Conclusions- We have found the first locus associated with leukocyte counts in ischemic stroke, also associated with acute outcome. Genetic analysis of acute endophenotypes could be useful to find the genetic factors associated with stroke outcome. Our findings suggested a different modulation of immune cells in stroke compared with healthy conditions.

Impact of a Training Intervention on the Pain Assessment in Advanced Dementia (PAINAD) Scale in Noncommunicative Inpatients.

BACKGROUND: Public hospitals in Catalonia (Spain) recommend using the Spanish version of the Pain Assessment in Advanced Dementia (PAINAD-Sp) scale for assessing pain in adult patients unable to self-report. However, since its inclusion in Catalonian nursing care plans in 2010, there have been no training programs for nurses, contributing to its current underuse. AIMS: The aim of this study was to assess the impact of a nurse training intervention on the PAINAD-Sp scale in noncommunicative inpatients unable to self-report. DESIGN: Before-after study. SETTINGS: Two public hospitals in Catalonia (Spain). PARTICIPANTS/SUBJECTS: Four hundred and one nurses participated in the training course and 219 patients received PAINAD-Sp assessments. METHODS: We used a before-after study design, evaluating the use of the PAINAD-Sp scale over two 6-month periods before and after an online training intervention for nurses in February 2017, in two public hospitals. Data were collected from patient records in each center. The primary outcome was the number of patients receiving PAINAD-Sp assessments during admission. Secondary outcomes were the number of assessments undertaken per patient during admission, the total (0-10) and item-specific (0-2) PAINAD-Sp score, and pharmacologic treatment administered. RESULTS: There were 401 nurses who took part in the training program. Over the study period, 219 patients received PAINAD-Sp assessments: 29 in the preintervention period and 190 in the postintervention period (p < .001). Administration of analgesics and antipyretics decreased (p < .001) after the intervention, whereas use of hypnotic drugs and sedatives increased. CONCLUSIONS: Theoretical and practical training may be an effective way to improve nurses' approach to identifying, assessing, and managing pain in patients unable to self-report.

Validation of the Spanish Version of the Pain Assessment in Advanced Dementia Scale (PAINAD-Sp) in Hospitalized Patients with Neurologic Disorders and Oncologic Patients Unable to Self-Report Their Pain.

BACKGROUND: Pain has a significant impact on hospitalized patients and is a quality indicator for nursing care. The Pain Assessment in Advanced Dementia (PAINAD) scale measures pain in people with communication disorders and advanced dementia, but it has not been validated in any other population. AIMS: The aim of this study was to validate the Spanish version (PAINAD-Sp) in hospitalized patients with neurologic disorders and in end-of-life cancer patients with difficulty self-reporting. DESIGN: The study had two phases: (1) analysis of the content by a committee of experts and (2) a cross-sectional study. SETTINGS: We collected phase 2 data from January 2017 to December 2017 in four hospitals in Barcelona: Hospital Germans Trias i Pujol, Institut Català d'Oncologia, Hospital Vall d'Hebron, and Hospital de Bellvitge. PARTICIPANTS/SUBJECTS: We included all adults who had either a neurological disorder affecting language or an oncological disease with an end-of-life prognosis and difficulty self-reporting pain. We excluded patients with a diagnosis of dementia. METHODS: The cross-sectional study included 325 patients who were simultaneously evaluated by two observers both at rest and in movement. We analyzed psychometric properties in terms of construct validity, reliability, and sensitivity to change. RESULTS: We obtained Cronbach α > .70 in both situations and an inter-rater reliability of 0.80. Confirmatory factor analysis indicated that the model adjusted adequately to a unidimensional structure. In terms of sensitivity to change, the mean difference was greater in movement than at rest (difference in means was 1.15). CONCLUSIONS: The PAINAD-Sp_Hosp scale had good psychometric qualities in terms of validity and reliability in neurology and oncology patients unable to self-report pain.

Reported Prestroke Physical Activity Is Associated with Vascular Endothelial Growth Factor Expression and Good Outcomes after Stroke.

INTRODUCTION: Physical activity (PhA) prior to stroke has been associated with good outcomes after the ischemic insult, but there is scarce data on the involved molecular mechanisms. METHODS: We studied consecutive acute ischemic stroke patients admitted to a single tertiary stroke center. Prestroke PhA was evaluated with the International Physical Activity Questionnaire (metabolic equivalent of minutes/week). We studied several circulating angiogenic and neurogenic factors at different time points: vascular endothelial growth factor (VEGF), granulocyte colony-stimulating factor (G-CSF), and brain-derived neurotrophic factor (BDNF) at admission, day 7, and at 3 months. We considered good functional outcome at 3 months (modified Rankin scale ≤ 2) as primary end point, and final infarct volume as secondary outcome. RESULTS: We studied 83 patients with at least 2 time point serum determinations (mean age 69.6 years, median National Institutes of Health Stroke Scale 17 at admission). Patients more physically active before stroke had a significantly higher increment of serum VEGF on the seventh day when compared to less active patients. This increment was an independent predictor of good functional outcome at 3 months and was associated with smaller infarct volume in multivariate analyses adjusted for relevant covariates. We did not find independent associations of G-CSF or BDNF levels neither with level of prestroke PhA nor with stroke outcomes. CONCLUSIONS: Although there are probably more molecular mechanisms by which PhA exerts its beneficial effects in stroke outcomes, our observation regarding the potential role of VEGF is plausible and in line with previous experimental studies. Further research in this field is needed.

Comparison of elevated intracranial pressure pulse amplitude and disproportionately enlarged subarachnoid space (DESH) for prediction of surgical results in suspected idiopathic normal pressure hydrocephalus.

BACKGROUND: To compare the prognostic value of pulse amplitude on intracranial pressure (ICP) monitoring and disproportionately enlarged subarachnoid space hydrocephalus (DESH) on magnetic resonance imaging (MRI) for predicting surgical benefit after shunt placement in idiopathic normal pressure hydrocephalus (iNPH). METHOD: Patients with suspected iNPH were prospectively recruited from a single centre. All patients received preoperative MRI and ICP monitoring. Patients were classified as shunt responders if they had an improvement of one point or more on the NPH score at 1 year post-surgery. The sensitivity, specificity, Youden index, and positive and negative predictive values of the two diagnostic methods were calculated. RESULTS: Sixty-four of 89 patients clinically improved at 1 year post-surgery and were classed as shunt responders. Positive DESH findings had a sensitivity of 79.4 % and specificity of 80.8 % for predicting shunt responders. Fifty-five of 89 patients had positive DESH findings: 50 of these responded to VP shunt, giving a positive and negative predictive value of 90.9 % and 61.8 %, respectively. Fifty-seven of 89 patients had high ICP pulse amplitude. High ICP pulse amplitude had a sensitivity of 84.4 %, specificity of 88 %, positive predictive value of 94.7 % and negative predictive value of 61.8 % for predicting shunt responders. CONCLUSIONS: Both positive DESH findings and high ICP pulse amplitude support the diagnosis of iNPH and provide additional diagnostic value for predicting shunt-responsive patients; however, high ICP amplitude was more accurate than positive DESH findings, although it is an invasive test.