On the Potential Benefit of Shunt Surgery in Idiopathic Normal-Pressure Hydrocephalus Patients with Alzheimer's Disease Pathology
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ABSTRACT:
SUBMITTER: Kang K
PROVIDER: S-EPMC8585530 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We aimed to determine whether presence of AD neuropathology predicted cognitive, gait and balance measures in patients with idiopathic normal pressure hydrocephalus (iNPH) after shunt surgery. This is a prospective study of gait and balance measured by Timed Up and Go (TUG) and Tinetti tests, and cognitive function measured by Mini Mental Status Exam (MMSE), before and after shunt surgery in participants 65 years and older with iNPH at the Johns Hopkins University. Random effects models were used and adjusted for confounders. 88 participants were included in the analysis with a median (IQR) time of 104 (57-213) days between surgery and follow-up. 23 (25%) participants had neuritic plaques present (NP+) and were significantly older [76.4 (6.0) years], but were otherwise similar in all demographics and outcome measures, when compared to the group without neuritic plaques (NP-). NP- and NP+ participants equally improved on measures of TUG (β = -3.27, 95% CI -6.24, -0.30, p = 0.03; β = -2.37, 95% CI -3.90, -0.86, p = 0.02, respectively), Tinetti-total (β = 1.95, 95% CI 1.11, 2.78, p<0.001; β = 1.72, 95% CI 0.90, 2.53, p<0.001, respectively), -balance (β = 0.81, 95% CI 0.23, 1.38, p = 0.006; β = 0.87, 95% CI 0.40, 1.34, p<0.001, respectively) and -gait (β = 1.03, 95% CI 0.61, 1.45, p<0.001; β = 0.84, 95% CI 0.16, 1.53, p = 0.02, respectively), while neither NP- nor NP+ showed significant improvement on MMSE (β = 0.10, 95% CI -0.27, 0.46, p = 0.61, β = 0.41, 95% CI -0.27, 1.09, p = 0.24, respectively). In summary, 26% of participants with iNPH had coexisting AD pathology, which does not significantly influence the clinical response to shunt surgery.
| S-EPMC5546572 | biostudies-other
Project description:Background and purposeTo examine the effect of delayed compared to early planning of shunt surgery on survival, in patients with idiopathic normal pressure hydrocephalus (iNPH), a long-term follow-up case-control study of patients exposed to a severe delay of treatment was performed.MethodsIn 2010-2011 our university hospital was affected by an administrative and economic failure that led to postponement of several elective neurosurgical procedures. This resulted in an unintentional delay of planning of treatment for a group of iNPH patients, referred to as iNPHDelayed (n = 33, waiting time for shunt surgery 6-24 months). These were compared to patients treated within 3 months, iNPHEarly (n = 69). Primary outcome was mortality. Dates and underlying causes of death were provided by the Cause of Death Registry. Survival was analysed by Kaplan-Meier plots and a Cox proportional hazard model adjusted for potential confounders.ResultsMedian follow-up time was 6.0 years. Crude 4-year mortality was 39.4% in iNPHDelayed compared to 10.1% in iNPHEarly (p = 0.001). The adjusted hazard ratio in iNPHDelayed was 2.57; 95% confidence interval 1.13-5.83, p = 0.024. Causes of death were equally distributed between the groups except for death due to malignancy which was not seen in iNPHDelayed but in 4/16 cases in iNPHEarly (p = 0.044).ConclusionsThe present data indicate that shunt surgery is effective in iNPH and that early treatment increases survival.
| S-EPMC7986742 | biostudies-literature
Project description:Background:The 3-meter Timed Up and Go test (TUG) is a reliable quantitative test for assessment of gait and balance. We aimed to establish an optimal threshold of TUG at the tap test for predicting outcomes 12 months after shunt surgery in patients with idiopathic normal pressure hydrocephalus (iNPH). Methods:The TUG was measured in a total of 151 patients with possible iNPH before and after a tap test and 12 months after shunt surgery. Among them, 81 patients underwent ventriculoperitoneal shunt implantation (SINPHONI) and 70 underwent lumboperitoneal shunt implantation (SINPHONI-2). The areas under the curve (AUCs), sensitivities, and specificities for predicting shunt effectiveness were assessed. Results:The simple differences of time on TUG at the tap test were significantly more accurate for predicting shunt effectiveness than percent improvement of time. The highest AUC for the synchronized moving cutoff point of TUG time was 0.81 (sensitivity 81.0%; specificity 81.6%) at the threshold of 5 seconds in the SINPHONI-2. For predicting improvements of ?10 seconds 12 months after lumboperitoneal shunt implantation, the AUC was 0.90, and the sensitivity and specificity at the threshold of 5.6 seconds were 83.3% and 81.0%. Only for patients with a <5-second improvement at the tap test, ventriculoperitoneal shunt implantation conveyed significantly better improvements in TUG time 12 months after surgery than lumboperitoneal shunt implantation. Conclusions:An improvement of 5 seconds was a useful threshold of TUG time at the tap test for predicting a ?10-second improvement 12 months after shunt surgery, rather than the percent improvement of TUG time.
| S-EPMC5669413 | biostudies-literature
Project description:The long-term prognosis of cognitive function in patients with idiopathic normal pressure hydrocephalus (iNPH) remains unclear. This study aimed to determine the long-term prognosis of cognitive function in patients with iNPH, as well as the factors related to it. It included 48 patients with iNPH who were treated with cerebrospinal fluid shunting between January 2015 and December 2017 at Osaka Medical College Hospital, with follow-up evaluation of their cognitive function for >2 years. Cognitive function was measured using the Mini-Mental State Examination (MMSE) preoperatively and at 3 months, 1 and 2 years post-operatively. The mean MMSE score (22.4 ± 5.4 preoperatively) improved at 3 months [23.8 ± 5.0 (p = 0.0002)] and 1 year [23.7 ± 4.8 (p = 0.004)] post-operatively. At 2 years post-operatively, they were able to maintain their preoperative level (22.6 ± 5.3). The patients were classified in to the cognitive decline group [11 (23%) patients; a decrease in the MMSE score by ≥ 2 points 2 years after surgery] and the maintenance/improvement group [37 (77%) patients]. Univariate and receiver operating characteristic analyses were performed for the two groups to identify factors associated with cognitive prognosis. In both groups, the patients who were younger (p = 0.009) or had milder symptoms (p = 0.035) had a better long-term prognosis of cognitive function. The cutoffs for age and disease severity (idiopathic normal-pressure hydrocephalus grading scale; INPHGS) were 78 years (area under the curve = 0.77) and 5 points (area under the curve = 0.71), respectively. In conclusion, most patients (77%) were able to improve and maintain cognitive function for at least 2 years after surgery. The fact that disease severity and age are associated with cognitive prognosis suggests that early iNPH intervention is desirable to improve cognitive prognosis.
| S-EPMC7854532 | biostudies-literature
Project description:Molecular biomarkers for neurodegenerative diseases are critical for advancing diagnosis and therapy. Normal pressure hydrocephalus (NPH) is a neurological disorder characterized by progressive neurodegeneration, gait impairment, urinary incontinence and cognitive decline. In contrast to most other neurodegenerative disorders, NPH symptoms can be improved by the placement of a ventricular shunt that drains excess CSF. A major challenge in NPH management is the identification of patients who benefit from shunt surgery. Here, we perform genome-wide RNA sequencing of extracellular vesicles in CSF of 42 NPH patients, and we identify genes and pathways whose expression levels correlate with gait, urinary or cognitive symptom improvement after shunt surgery. We describe a machine learning algorithm trained on these gene expression profiles to predict shunt surgery response with high accuracy. The transcriptomic signatures we identified may have important implications for improving NPH diagnosis and treatment and for understanding disease aetiology.
2023-06-02 | GSE212236 | GEO
Project description:Background Rehabilitation in iNPH is suggested to be an important factor to improve patients’ functions but there are lack of clinical trials evaluating the effect of rehabilitation interventions after shunt surgery in iNPH. The objective of this study was to evaluate the effect of a physical exercise programme and goal attainment for patients with idiopathic normal pressure hydrocephalus (iNPH) after surgery compared to a control group. Methods This was a dual centre randomised controlled trial with assessor blinding, intention-to-treat (ITT) and per protocol (PP) analysis. Individuals diagnosed with iNPH scheduled to undergo shunt surgery at the Linköping University Hospital in Linköping and Sahlgrenska University Hospital in Gothenburg, Sweden were consecutively eligible for inclusion. Inclusion was conducted between January 2016 and June 2018. The patients were randomised 1:1 using sequentially numbered sealed envelopes to receive either written exercise information (control group) or written information and an additional supervised high-intensity, functional exercise programme (HIFE) executed twice weekly over 12 weeks (exercise group). Preoperatively, the patients set individual goals. The primary outcome was change from baseline in the total iNPH scale score at the post-intervention follow-up. Secondary outcomes were goal attainment, and change in the separate scores of gait, balance, neuropsychology and continence and in the total score after 6 months. Results In total, 127 participants were randomised to the exercise group (n = 62) and to the control group (n = 65). In the ITT population (exercise group, n = 50; control group, n = 59), there were no between-group differences in the primary outcome, but the attrition rate in the exercise group was high. The exercise group improved more than the control group in the balance domain scores after 6 months. Post-intervention, the PP exercise population achieved their set goals to a greater extent than the controls. Conclusions An additional effect of the 12-week HIFE-programme on the overall improvement according to the iNPH-scale after shunt surgery in iNPH was not shown. This could be due to high attrition rate. However, the long-term effect on balance and higher goal achievement indicate beneficial influences of supervised physical exercise. Trial registration clinicaltrials.gov, NCT02659111. Registered 20 January 2016, https://clinicaltrials.gov/ct2/show/NCT02659111 Supplementary Information The online version contains supplementary material available at 10.1186/s12987-021-00287-8.
| S-EPMC8607575 | biostudies-literature
Project description:Idiopathic normal pressure hydrocephalus (iNPH) is a syndrome characterized by gait disturbance, cognitive deterioration and urinary incontinence in elderly individuals. These symptoms can be improved by shunt operation in some but not all patients. Therefore, discovering predictive factors for the surgical outcome is of great clinical importance. We used normalized power variance (NPV) of electroencephalography (EEG) waves, a sensitive measure of the instability of cortical electrical activity, and found significantly higher NPV in beta frequency band at the right fronto-temporo-occipital electrodes (Fp2, T4 and O2) in shunt responders compared to non-responders. By utilizing these differences, we were able to correctly identify responders and non-responders to shunt operation with a positive predictive value of 80% and a negative predictive value of 88%. Our findings indicate that NPV can be useful in noninvasively predicting the clinical outcome of shunt operation in patients with iNPH.
| S-EPMC4293598 | biostudies-other
Project description:The present study aimed to examine time-dependent change in cerebrospinal fluid distribution and various radiological indices for evaluating shunt effectiveness in patients with idiopathic normal pressure hydrocephalus (iNPH). This study included 54 patients with iNPH who underwent MRI before and after ventriculoperitoneal shunt surgery. The volume of the total ventricles and subarachnoid spaces decreased within 1 month after shunting. However, more than 1 year after shunting, the volume of the total ventricles decreased, whereas that of the total subarachnoid spaces increased. Although cerebrospinal fluid distribution changed considerably throughout the follow-up period, the brain parenchyma expanded only 2% from the baseline brain volume within 1 month after shunting and remained unchanged thereafter. The volume of the convexity subarachnoid space markedly increased. The changing rate of convexity subarachnoid space per ventricle ratio (CVR) was greater than that of any two-dimensional index. The brain per ventricle ratio (BVR), callosal angle and z-Evans index continued gradually changing, whereas Evans index did not change throughout the follow-up period. Both decreased ventricular volume and increased convexity subarachnoid space volume were important for evaluating shunt effectiveness. Therefore, we recommend CVR and BVR as useful indices for the diagnosis and evaluation of treatment response in patients with iNPH.
| S-EPMC6872815 | biostudies-literature
Project description:ObjectivesIdiopathic normal pressure hydrocephalus (INPH) is a neurodegenerative disorder characterized by excess cerebrospinal fluid (CSF) in the ventricles, which can be diagnosed by invasive CSF drainage test and treated by shunt placement. Here, we aim to investigate the diagnostic and prognostic power of systematic volumetric analysis based on brain structural MRI for INPH.MethodsWe performed a retrospective study with a cohort of 104 probable INPH patients who underwent CSF drainage tests and another cohort of 41 INPH patients who had shunt placement. High-resolution T1-weighted images of the patients were segmented using an automated pipeline into 283 structures that are grouped into different granularity levels for volumetric analysis. Volumes at multi-granularity levels were used in a recursive feature elimination model to classify CSF drainage responders and non-responders. We then used pre-surgical brain volumes to predict Tinetti and MMSE scores after shunting, based on the least absolute shrinkage and selection operator.ResultsThe classification accuracy of differentiating the CSF drainage responders and non-responders increased as the granularity increased. The highest diagnostic accuracy was achieved at the finest segmentation with a sensitivity/specificity/precision/accuracy of 0.89/0.91/0.84/0.90 and an area under the curve of 0.94. The predicted post-surgical neurological scores showed high correlations with the ground truth, with r = 0.80 for Tinetti and r = 0.88 for MMSE. The anatomical features that played important roles in the diagnostic and prognostic tasks were also illustrated.ConclusionsWe demonstrated that volumetric analysis with fine segmentation could reliably differentiate CSF drainage responders from other INPH-like patients, and it could accurately predict the neurological outcomes after shunting.Key points• We performed a fully automated segmentation of brain MRI at multiple granularity levels for systematic volumetric analysis of idiopathic normal pressure hydrocephalus (INPH) patients. • We were able to differentiate patients that responded to CSF drainage test with an accuracy of 0.90 and area under the curve of 0.94 in a cohort of 104 probable INPH patients, as well as to predict the post-shunt gait and cognitive scores with a coefficient of 0.80 for Tinetti and 0.88 for MMSE. • Feature analysis showed the inferior lateral ventricle, bilateral hippocampus, and orbital cortex are positive indicators of CSF drainage responders, whereas the posterior deep white matter and parietal subcortical white matter were negative predictors.
| S-EPMC8213563 | biostudies-literature
Project description:BackgroundIn patients with idiopathic normal pressure hydrocephalus (iNPH) responding to shunt surgery, we have consistently found elevated intracranial pressure (ICP) wave amplitudes during diagnostic ICP monitoring prior to surgery. It remains unknown why ICP wave amplitudes are increased in these patients. Since iNPH is accompanied by a high incidence of vascular co-morbidity, a possible explanation is that there is reduced vascular compliance accompanied by elevated arterial blood pressure (ABP) wave amplitudes and even altered cardiac output (CO). To investigate this possibility, the present study was undertaken to continuously monitor CO to determine if it is correlated to ABP and ICP wave amplitudes and the outcome of shunting in iNPH patients. It was specifically addressed whether the increased ICP wave amplitudes seen in iNPH shunt responders were accompanied by elevated CO and/or ABP wave amplitude levels.MethodsProspective iNPH patients (29) were clinically graded using an NPH grading scale. Continuous overnight minimally-invasive monitoring of CO and ABP was done simultaneously with ICP monitoring; the CO, ABP, and ICP parameters were parsed into 6-second time windows. Patients were assessed for shunt surgery on clinical grade, Evan's index, and ICP wave amplitude. Follow-up clinical grading was performed 12 months after surgery.ResultsICP wave amplitudes but not CO or ABP wave amplitude, showed good correlation with the response to shunt treatment. The patients with high ICP wave amplitude did not have accompanying high levels of CO or ABP wave amplitude. Correlation analysis between CO and ICP wave amplitudes in individual patients showed different profiles [significantly positive in 10 (35%) and significantly negative in 16 (55%) of 29 recordings]. This depended on whether there was also a correlation between ABP and ICP wave amplitudes and on the average level of ICP wave amplitude.ConclusionsThese results gave no evidence that the increased levels of ICP wave amplitudes seen in iNPH shunt responders prior to surgery were accompanied by elevated levels of ABP wave amplitudes or elevated CO. In the individual patients the correlation between CO and ICP wave amplitude was partly related to an association between ABP and ICP wave amplitudes which can be indicative of the state of cerebrovascular pressure regulation, and partly related to the ICP wave amplitude which can be indicative of the intracranial compliance.
| S-EPMC3044095 | biostudies-literature