Tag: iNPH

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Vascular risk profiles for predicting outcome and long-term mortality in patients with idiopathic normal pressure hydrocephalus: comparison of clinical decision support tools

J Neurosurg 138:476–482, 2023

Vascular risk factors (VRFs) may act synergistically, and clinical decision support tools (CDSTs) have been developed that present vascular risk as a summarized score. Because VRFs are a major issue in patients with idiopathic normal pressure hydrocephalus (INPH), a CDST may be useful in the diagnostic workup. The objective was to compare 4 CDSTs to determine which one most accurately predicts short-term outcome and 10-year mortality after CSF shunt surgery in INPH patients.

METHODS One-hundred forty INPH patients who underwent CSF shunt surgery were included. For each patient, 4 CDST scores (Systematic Coronary Risk Evaluation–Older Persons [SCORE-OP], Framingham Risk Score [FRS], Revised Framingham Stroke Risk Profile, and Kiefer’s Comorbidity Index [KCI]) were estimated. Short-term outcome (3 months after CSF shunt surgery) was defined on the basis of improvements in gait, Mini-Mental State Examination score, and modified Rankin Scale score. The 10-year mortality rate after surgery was noted. The CDSTs were compared by using Cox regression analysis, receiver operating characteristic curve analysis, and the chi-square test.

RESULTS For 3 CDSTs, increased score was associated with increased risk of 10-year mortality. A 1-point increase in the FRS indicated a 2% higher risk of death within 10 years (HR 1.02, 95% CI 1.003–1.035, p = 0.021); SCORE-OP, 5% (HR 1.05, 95% CI 1.019–1.087, p = 0.002); and KCI, 12% (HR 1.12, 95% CI 1.03–1.219, p = 0.008). FRS predicted short-term outcome of surgery (p = 0.024). When the cutoff value was set to 32.5%, the positive predictive value was 80% and the negative predictive value was 48% (p = 0.012).

CONCLUSIONS The authors recommend using FRS to predict short-term outcome and 10-year risk of mortality in INPH patients. The study indicated that extensive treatment of the risk factors of INPH may decrease risk of mortality.

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Cerebrospinal fluid and venous biomarkers of shunt‐responsive idiopathic normal pressure hydrocephalus: a systematic review and meta‐analysis

Acta Neurochirurgica (2022) 164:1719–1746

Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease and dementia subtype involving disturbed cerebrospinal fluid (CSF) homeostasis. Patients with iNPH may improve clinically following CSF diversion through shunt surgery, but it remains a challenge to predict which patients respond to shunting. It has been proposed that CSF and blood biomarkers may be used to predict shunt response in iNPH.

Objective To conduct a systematic review and meta-analysis to identify which CSF and venous biomarkers predict shunt- responsive iNPH most accurately.

Methods Original studies that investigate the use of CSF and venous biomarkers to predict shunt response were searched using the following databases: Embase, MEDLINE, Scopus, PubMed, Google Scholar, and JSTOR. Included studies were assessed using the ROBINS-I tool, and eligible studies were evaluated utilising univariate meta-analyses.

Results The study included 13 studies; seven addressed lumbar CSF levels of amyloid-β 1–42, nine studies CSF levels of Total-Tau, six studies CSF levels of Phosphorylated-Tau, and seven studies miscellaneous biomarkers, proteomics, and genotyping. A meta-analysis of six eligible studies conducted for amyloid-β 1–42, Total-Tau, and Phosphorylated-Tau demonstrated significantly increased lumbar CSF Phosphorylated-Tau (− 0.55 SMD, p = 0.04) and Total-Tau (− 0.50 SMD, p = 0.02) in shunt-non-responsive iNPH, though no differences were seen between shunt responders and non-responders for amyloid-β 1–42 (− 0.26 SMD, p = 0.55) or the other included biomarkers.

Conclusion This meta-analysis found that lumbar CSF levels of Phosphorylated-Tau and Total-Tau are significantly increased in shunt non-responsive iNPH compared to shunt-responsive iNPH. The other biomarkers, including amyloid-β 1–42, did not significantly differentiate shunt-responsive from shunt-non-responsive iNPH. More studies on the Tau proteins examining sensitivity and specificity at different cut-off levels are needed for a robust analysis of the diagnostic efficiency of the Tau proteins.

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Motor skills, cognitive impairment, and quality of life in normal pressure hydrocephalus: early effects of shunt placement

Traditionally, clinical findings of normal pressure hydrocephalus are mainly characterized by the Hakim triad. The aim of this study is to evaluate the performance of patients suffering from idiopathic normal pressure hydrocephalus (iNPH) in a more holistic manner regarding motor skills, cognitive impairment, and quality of life.

Methods In total, 30 individuals diagnosed with iNPH as well as a reference group with another 30 individuals were included. The iNPH patients and the reference group were age, educational, and morbidity matched. A standardized test battery for psychomotor skills, gait, neuropsychological abilities as well as questionnaires for quality of life was applied. The iNPH group was tested prior to surgery, at 6 weeks, and 3 months postoperatively. The reference group was tested once.

Results Patients showed a significant improved performance in various items of the test battery during the first 3 months postoperatively. This included neuropsychological evaluation, motor skills including gait and upper motor function as well as the quality of life of the patients. Compared to reference individuals, neuropsychological aspects and quality of life of iNPH patients improved in some parts nearly to normal values.

Conclusion Our findings underline that shunt surgery does not only improve the symptoms in iNPH patients but also ameliorates the quality of life to a great extent close to those of age and comorbidity matched reference individuals. This data enables an optimized counseling of iNPH patients regarding the expectable outcome after shunt surgery especially regarding cognitive performance, motor skills as well as life quality.

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Cost-effectiveness analysis of shunt surgery for idiopathic normal pressure hydrocephalus

Acta Neurochir (2017) 159:995–1003

We showed that ventriculoperitoneal (VP) shunt and lumboperitoneal (LP) shunt surgeries are beneficial for patients with idiopathic normal pressure hydrocephalus (iNPH) in the Study of Idiopathic Normal Pressure Hydrocephalus on Neurological Improvement (SINPHONI; a multicenter prospective cohort study) and in SINPHONI-2 (a multicenter randomized trial). Although therapeutic efficacy is important, cost-effectiveness analysis is equally valuable.

Methods Using both a set of assumptions and using the data from SINPHONI and SINPHONI-2, we estimated the total cost of treatment for iNPH, which consists of medical expenses (e.g., operation fees) and costs to the long-term care insurance system (LCIS) in Japan. Regarding the natural course of iNPH patients, 10% or 20% of patients on each modified Rankin Scale (mRS) show aggravation (aggravation rate: 10% or 20%) every 3 months if the patients do not undergo shunt surgery, as described in a previous report. We performed cost-effectiveness analyses for the various scenarios, calculating the quality-adjusted life year (QALY) and the incremental cost-effective ratio (ICER). Then, based on the definition provided by a previous report, we assessed the cost-effectiveness of shunt surgery for iNPH.

Results In the first year after shunt surgery, the ICER of VP shunt varies from 29,934 to 40,742 USD (aggravation rate 10% and 20%, respectively) and the ICER of LP shunt varies from 58,346 to 80,392 USD (aggravation rate 10% and 20%, respectively), which indicates that the shunt surgery for iNPH is a cost-effective treatment. In the 2nd postoperative year, the cost to the LCIS will continue to decrease because of the lasting improvement of the symptoms due to the surgery. The total cost for iNPH patients will show a positive return on investment in as soon as 18 months (VP) and 21 months (LP), indicating that shunt surgery for iNPH is a cost-effective treatment.

Conclusions Because the total cost for iNPH patients will show a positive return on investment within 2 years, shunt surgery for iNPH is a cost-effective treatment and therefore recommended. The SINPHONI-2 study was registered with the University Hospital Medical Information Network Clinical Trials registry: UMIN000002730) SINPHONI was registered with ClinicalTrials.gov, no. NCT00221091.

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Different Patterns of Fornix Damage in Idiopathic Normal Pressure Hydrocephalus and Alzheimer Disease

Am J Neuroradiol 33:274 –79  Feb 2012

The fornix contains efferent fibers of the hippocampus and is in close contact with the corpus callosum. Part of the fornix is directly attached to the corpus callosum, and another part is suspended from the corpus callosum via the septum pellucidum. DTI can be used to evaluate the morphology and microstructural integrity of the fornix. We examined the pattern of fornix damage in patients with iNPH or AD.
MATERIALS AND METHODS: We enrolled 22 patients with iNPH, 20 with AD, and 20 healthy controls. DTI data were obtained. The morphology (volume, length, and mean cross-sectional area) and FA values of the fornix were evaluated by using tract-specific analysis and compared among groups.
RESULTS: The volume, cross-sectional area, and FA value of the fornix were significantly smaller in patients with iNPH than in controls, whereas the length was significantly greater. In patients with AD, the volume, mean cross-sectional area, and FA value of the fornix were significantly smaller than those in controls, whereas the length was not altered. The fornix was significantly longer in patients with iNPH than in patients with AD, whereas the volume and cross-sectional areas were significantly smaller.
CONCLUSIONS: Our results suggest that the different pathogeneses of these diseases lead to fornix damage through different mechanisms: through mechanical stretching due to lateral ventricular enlargement and corpus callosum deformation in patients with iNPH, and through degeneration secondary to hippocampal atrophy in patients with AD.

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Diffusion Tensor Imaging in Patients With Adult Chronic Idiopathic Hydrocephalus

Neurosurgery 66:917-924, 2010 DOI: 10.1227/01.NEU.0000367801.35654.EC

Diffusion tensor imaging (DTI) parameters were investigated in patients with chronic idiopathic hydrocephalus to evaluate microstructural changes of brain tissue caused by chronic ventricular dilatation.

METHODS: Eleven patients fulfilling the criteria for possible or probable idiopathic normal pressure hydrocephalus and 10 healthy control subjects underwent MRI at 3 Tesla, including DTI with 12 gradient directions. Patients were scanned before lumbar cerebrospinal fluid (CSF) withdrawal tests. Differences in fractional anisotropy (FA) and mean diffusivity (MD) between patients and controls were assessed using 2 different methods: manual definition of regions of interest and a fully automated method, TBSS (Tract-Based Spatial Statistics). DTI parameters were correlated with clinical findings.

RESULTS: Compared with the control group, patients with chronic idiopathic hydrocephalus had significantly higher MD values in both the periventricular corticospinal tract (CST) and the corpus callosum (CC), whereas FA values were significantly higher in the CST but lower in the CC. DTI parameters of the CST correlated with the severity of gait disturbances.

CONCLUSION:Microstructural changes in periventricular functionally relevant white matter structures (CSF, CC) in chronic idiopathic hydrocephalus can be visualized using DTI. Further studies should investigate the change of DTI parameters after CSF shunting and its relation to neurologic outcome.

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