Ventriculoperitoneal shunt patients and glaucoma: a cohort analysis of the NPH registry.

BACKGROUND: Idiopathic Normal Pressure Hydrocephalus (iNPH) is a chronic condition affecting the elderly. It is characterized by a triad of symptoms and radiological findings. Glaucoma is the leading cause of irreversible blindness worldwide. Earlier studies have proposed that the rate of glaucoma is higher in iNPH patients, and of a possible link between ventriculoperitoneal shunt (VP) treatment and the development of glaucoma. OBJECTIVES: This study aimed to determine the prevalence of glaucoma among iNPH patients and assess the impact of VPs on glaucoma prevalence. METHODS: A cohort study was conducted at Kuopio University Hospital (KUH), including 262 patients with a ventriculoperitoneal shunt. Clinical data were obtained from the Kuopio NPH Registry and medical records. Patients were grouped by iNPH status: iNPH (+) - probable/possible iNPH (n = 192), and iNPH (-) - other causes of hydrocephalus (congenital, secondary, obstructive) (n = 70). We conducted statistical analysis using the Independent Samples T-test, Fisher's exact test, and Pearson Chi-Square. We compared demographics, glaucoma prevalence, brain biopsies positive for Amyloid-ß (Aß) and hyperphosphorylated tau (HPτ) as well as comorbidities for hypertension and diabetes medication. Age stratification assessed glaucoma prevalence in the full cohort. RESULTS: Both iNPH (+) and iNPH (-) groups had comparable demographic and comorbidity profiles. The prevalence of glaucoma in the iNPH (+) group was 11.5% (n = 22) and 11.4% (n = 8) in the iNPH (-) group without a statistically significant difference (p = 1.000). Brain biopsies positive for Amyloid-ß (Aß) and hyperphosphorylated tau (HPτ) were similar. CONCLUSIONS: Neither shunted iNPH patients nor those with a comorbid condition other than iNPH showed a markedly higher prevalence of glaucoma. Instead, both groups exhibited age-related increases in glaucoma prevalence, similar to the trends observed in population-based studies. Our data does not suggest a correlation between VP shunts and an elevated rate of glaucoma.

Prognostic Factors in Idiopathic Normal Pressure Hydrocephalus Patients After Ventriculo-Peritoneal Shunt: Results from a Single-Institution Observational Cohort Study with Long Term Follow-Up.

OBJECTIVE: The aim of this study is to investigate long-term prognostic factors and clinical outcomes in patients with idiopathic normal pressure hydrocephalus (iNPH) treated with ventriculo-peritoneal shunt (VPS). METHODS: This single-center retrospective observational study of prospectively collected data included patients with probable iNPH treated with VPS surgery. All patients underwent complete preoperative assessment, including past medical history and neurological examination, dynamic cerebrospinal fluid (CSF) flow brain magnetic resonance imaging (MRI), and preoperative CSF samplings. NPH-consistent brain MRI findings and favorable responses to CSF subtraction tests were the main factors considered for VPS surgery eligibility. All patients were subsequently followed up every six to twelve months (mean follow-up time 40 months, minimum to maximum interval 6-150 months). RESULTS: A total of 238 patients with a diagnosis of probable iNPH treated with VPS were enrolled. Age, comorbidities, and response to CSF samplings were not significantly associated with a better long-term outcome after VPS surgery. The results of our retrospective analysis demonstrated a statistically significant association between the presence of preoperative aqueductal CSF flow acceleration on dynamic brain MRI and neurological outcomes at 12 and 18 months after VPS surgery. CONCLUSIONS: Long-term outcomes of iNPH patients treated with VPS surgery do not appear to be directly influenced by preoperative comorbidities, age, or responses to CSF samplings. Alterations in preoperative brain MRI CSF dynamics were found to be related to long-term outcomes following VPS surgery, highlighting the role of radiological assessment as a prognostic factor in patients deemed suitable candidates for VPS surgery.

Is there a spinal tap responder in progressive supranuclear palsy? The first prospective study.

OBJECTIVE: Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disease, and sometimes shows idiopathic normal pressure hydrocephalus (iNPH)-like presentations. We aimed to evaluate spinal tap responsiveness in patients with PSP, including the effect of sham spinal tap. METHODS: Eleven patients with PSP, ten with probable/definite iNPH, and eight control patients were prospectively enrolled. All participants underwent sham spinal tap and spinal tap procedures. Gait was evaluated using wearable inertial sensors. We defined "tap responders" as individuals with a 10% or more improvement from baseline in any of the gait parameters (timed up-and-go test total time, stride length, and velocity during straight walking under single-task and cognitive dual-task conditions). We compared the ratio of responders in patients with PSP to patients with iNPH and controls. RESULTS: The ratio of tap responders and the ratio of sham tap responders in patients with PSP were significantly higher than those in control patients, and not different from those in patients with iNPH. PSP patients with iNPH-like MRI features tended to respond to the spinal tap compared to those without such imaging features. Notably, one patient with PSP, who responded to the spinal tap beyond the effect of sham spinal tap, was treated by the shunt operation. CONCLUSION: This is the first prospective study to demonstrate tap and shunt responsiveness in patients with PSP while highlighting the placebo effects of the spinal tap in patients with PSP or iNPH. Our findings suggest that some PSP patients have impaired cerebrospinal fluid circulation, contributing to a distinct component of the clinical spectrum.

Idiopathic normal pressure hydrocephalus: Validation of the DESH score as a prognostic tool for shunt surgery response.

OBJECTIVE: Several radiological markers have been linked to clinical improvement after shunt surgery for idiopathic normal pressure hydrocephalus (iNPH). However, iNPH has no pathognomonic feature, and patients are still diagnosed as probable, possible, or unlikely cases based on clinical symptoms, imaging findings, and invasive supplementary tests. The predictive value of the disproportionately enlarged subarachnoid space hydrocephalus (DESH) score is not yet conclusively determined, but it might offer a more accurate diagnostic method. The aim of the present retrospective cohort study was to validate the predictive power of the DESH score for clinical improvement after shunt surgery in iNPH patients. METHODS: We retrospectively obtained presurgical MRI and/or CT scans from 71 patients with iNPH who underwent ventriculoperitoneal shunt surgery. Radiological images were evaluated for Evans index (EI), corpus callosal angle (CA), tight high convexity (THC), Sylvian fissure dilation, and focal sulci dilation. These markers were aggregated to determine the DESH score. Patient journal entries were used to subjectively determine the extent of improvement in gait function, urinary incontinence, and/or cognition as a measure of shunt surgery response. RESULTS: Multiple logistic regression analysis, controlling for age and sex (α = 0.05), showed that DESH score was significantly correlated (OR 1.77) with subjective shunt-surgery response at a minimum of 1-month follow-up. Patients with higher DESH scores were more likely to have a favorable response to shunt surgery. CONCLUSION: Aggregating radiological markers into the DESH score is useful for predicting shunt responders among iNPH patients and can aid the selection of patients for surgery. These findings provide further support for the DESH score as a diagnostic tool for iNPH.

An Interdisciplinary Protocol for Ventriculoperitoneal Shunt Patient Selection in Normal Pressure Hydrocephalus.

BACKGROUND: Normal pressure hydrocephalus can be treated with ventriculoperitoneal shunt (VPS) placement, but no broadly implemented indication for VPS exists. METHODS: Our protocol consists of physical therapy and occupational therapy practitioners administering validated tests of gait, balance, and cognition before and after lumbar drain placement. Specific tests include: Timed "Up & Go", Tinetti Gait and Balance Assessment, Berg Balance Scale, Mini Mental Status Exam, Trail Making Test Part B, and the Rey Auditory and Visual Learning Test. Minimal clinically important difference values for each test were determined from literature review. A retrospective review of patients treated under this protocol was performed. The primary outcomes were candidacy for VPS based on the protocol and patient-reported symptomatic improvement after VPS placement. RESULTS: A total of 48/75 (64%) patients received VPS. A total of 43/48 (89.6%) of those shunted reported improved symptoms at 6-week follow-up. However, 10/22 (45.5%) reported worsening symptoms at 1-year follow-up. The mean Tinetti score significantly increased after lumbar drain in patients who improved with VPS compared to the no shunt group (4.27 vs. -0.48, P < 0.001). A total of 6/33 (18%) patients with postoperative imaging had a subdural fluid collection identified and 3/49 (6%) had other complications, including 1 seizure, 1 intracerebral hemorrhage, and 1 stroke. CONCLUSIONS: Standardized assessment of gait, balance, and cognition before and after temporary cerebrospinal fluid diversion identifies patients with normal pressure hydrocephalus likely to benefit from VPS placement with a low complication rate. One year after VPS, approximately one half of patients had symptoms recurrence.

Ventriculoperitoneal Shunt Placement Safety in Idiopathic Normal Pressure Hydrocephalus: Anticoagulated Versus Non-Anticoagulated Patients.

BACKGROUND: Many patients with idiopathic normal pressure hydrocephalus (iNPH) have medical comorbidities requiring anticoagulation that could negatively impact outcomes. This study evaluated the safety of ventriculoperitoneal shunt placement in iNPH patients on systemic anticoagulation versus those not on anticoagulation. METHODS: Patients >60 years of age with iNPH who underwent shunting between 2018 and 2022 were retrospectively reviewed. Baseline demographics, comorbidities (quantified by modified frailty index and Charlson comorbidity index), anticoagulant/antiplatelet agent use (other than aspirin), operative details, and complications were collected. Outcomes of interest were the occurrence of postoperative hemorrhage and overdrainage. RESULTS: A total of 234 patients were included in the study (mean age 75.22 ± 6.04 years; 66.7% male); 36 were on anticoagulation/antiplatelet therapy (excluding aspirin). This included 6 on Warfarin, 19 on direct Xa inhibitors, 10 on Clopidogrel, and 1 on both Clopidogrel and Warfarin. Notably, 70% of patients (164/234) used aspirin alone or combined with anticoagulation or clopidogrel. Baseline modified frailty index was similar between groups, but those on anticoagulant/antiplatelet therapy had a higher mean Charlson comorbidity index (2.67 ± 1.87 vs. 1.75 ± 1.84; P = 0.001). Patients on anticoagulants were more likely to experience tract hemorrhage (11.1 vs. 2.5%; P = 0.03), with no significant difference in the rates of intraventricular hemorrhage or overdrainage-related subdural fluid collection. CONCLUSIONS: Anticoagulant and antiplatelet agents are common in the iNPH population, and patients on these agents experienced higher rates of tract hemorrhage following ventriculoperitoneal shunt placement; however, overall hemorrhagic complication rates were similar.

The grasp reflex in patients with idiopathic normal pressure hydrocephalus.

OBJECTIVE: To investigate the prevalence and intensity of grasp reflexes and to examine changes in these reflexes after shunt surgery in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS: We enrolled 147 patients with probable iNPH. A standard procedure was used to determine the presence of grasp reflexes, and the intensity of these reflexes was assessed using a four-category classification. Clinical rating scales and their correlation with grasp reflexes were also evaluated. Grasp reflexes were reassessed in 72 patients 1 year after surgery. RESULTS: We found that approximately 50.3% of patients with iNPH exhibited a positive grasp reflex. Among these patients, 69% exhibited bilateral positivity, while the remaining patients showed unilateral positivity. Furthermore, the intensity of the grasp reflex was significantly correlated with the severity of gait and with cognitive, urinary, motor, and behavioural symptoms. Surgical interventions led to a reduction (41.7%) or maintenance (30.6%) of the reflex intensity in 72.3% of iNPH patients. The changes in reflex intensity showed significant positive correlations with changes in the number of steps of the Timed Up and Go test and Trail Making Test-A scores but not with changes in total scores on the iNPH Grading Scale. CONCLUSION: This retrospective study identified grasp reflexes as a highly prevalent phenomenon in patients with iNPH. These reflexes can assist in evaluating the severity of various symptoms, including cognitive, gait, urinary, motor and emotional symptoms.

Predicting post-surgical outcomes in idiopathic normal pressure hydrocephalus using clinically important changes from the cerebrospinal fluid tap test.

OBJECTIVE: Patients diagnosed with idiopathic Normal Pressure Hydrocephalus (iNPH) typically experience symptom improvements after undergoing a cerebrospinal fluid-tap test (CSF-TT), These improvements are recognized as indicative of potential improvements following surgical intervention. As gait disturbance is the most common iNPH symptom, gait improvements are of predominant interest. The purpose of this study was to examine if clinically important changes in gait and balance from CSF-TT predict meaningful changes following surgery. METHOD: The study involved analysis of data collected in a prospective observational study for 34 iNPH patients who underwent a CSF-TT and subsequent surgery. Linear regression, logistic regression and classification trees were used for predictive modelling comparing changes from CSF-TT with post-surgical changes in Tinetti, Timed Up and Go (TUG) and Berg Balance Scale (BBS) outcomes. RESULTS: Predictive models for minimal clinically important differences (MCIDs) from CSF-TT to surgery were significant for Tinetti (odds ratio = 1.42, p = 0.02) and BBS (odds ratio = 1.57, p < 0.01). Four items on Tinetti and two items on BBS were identified with a predictive accuracy of 79% and 76% respectively. BBS has the highest sensitivity (85%) and negative predictive value (77%). TUG had a 100% specificity and 100% positive predictive value. The predictive model using MCIDs for TUG was not significant (odds ratio = 1.13, p = 0.06). CONCLUSION: Clinically important changes from CSF-TT are useful in predicting post-surgical outcomes in iNPH patients. Tinetti and BBS, both have predictive value using MCID scores as cut off values, of which BBS is a stronger outcome measure for prediction.

Risk Analysis Index as a preoperative frailty tool for elective ventriculoperitoneal shunt surgery for idiopathic normal pressure hydrocephalus.

OBJECTIVE: Idiopathic normal pressure hydrocephalus (iNPH) predominantly occurs in older patients, and ventriculoperitoneal shunt (VPS) placement is the definitive surgical treatment. VPS surgery carries significant postoperative complication rates, which may tip the risk/benefit balance of this treatment option for frail, or higher-risk, patients. In this study, the authors investigated the use of frailty scoring for preoperative risk stratification for adverse event prediction in iNPH patients who underwent elective VPS placement. METHODS: The Nationwide Readmissions Database (NRD) was queried from 2018 to 2019 for iNPH patients aged ≥ 60 years who underwent VPS surgery. Risk Analysis Index (RAI) and modified 5-item Frailty Index (mFI-5) scores were calculated and RAI cross-tabulation was used to analyze trends in frailty scores by the following binary outcome measures: overall complications, nonhome discharge (NHD), extended length of stay (eLOS) (> 75th percentile), and mortality. Area under the receiver operating characteristic curve analysis was performed to assess the discriminatory accuracy of RAI and mFI-5 for primary outcomes. RESULTS: A total of 9319 iNPH patients underwent VPS surgery, and there were 685 readmissions (7.4%), 593 perioperative complications (6.4%), and 94 deaths (1.0%). Increasing RAI score was significantly associated with increasing rates of postoperative complications: RAI scores 11-15, 5.4% (n = 80); 16-20, 5.6% (n = 291); 21-25, 7.6% (n = 166); and ≥ 26, 11.6% (n = 56). The discriminatory accuracy of RAI was statistically superior (DeLong test, p < 0.05) to mFI-5 for the primary endpoints of mortality, NHD, and eLOS. All RAI C-statistics were > 0.60 for mortality within 30 days (C-statistic = 0.69, 95% CI 0.68-0.70). CONCLUSIONS: In a nationwide database analysis, increasing frailty, as measured by RAI, was associated with NHD, 30-day mortality, unplanned readmission, eLOS, and postoperative complications. Although the RAI outperformed the mFI-5, it is essential to account for the potentially reversible clinical issues related to the underlying disease process, as these factors may inflate frailty scores, assign undue risk, and diminish their utility. This knowledge may enhance provider understanding of the impact of frailty on postoperative outcomes for patients with iNPH, while highlighting the potential constraints associated with frailty assessment tools.

Efficacy and safety of shunt surgery in patients with idiopathic normal-pressure hydrocephalus: can we predict shunt response by preoperative magnetic resonance imaging (MRI)?

AIM: The aim of this study was to identify preoperative magnetic resonance imaging (MRI) findings that can predict the shunt responsiveness in idiopathic normal-pressure hydrocephalus (iNPH) patients and to investigate postoperative outcome and complications. MATERIALS AND METHODS: A total of 192 patients with iNPH who underwent shunt at our hospital between 2000 and 2021 were included to investigate complications. Of these, after exclusion, 127 (1-month postoperative follow-up) and 77 (1-year postoperative follow-up) patients were evaluated. The preoperative MRI features (the presence of tightness of the high-convexity subarachnoid space, Sylvian fissure enlargement, Evans' index, and callosal angle) of the shunt-response and nonresponse groups were compared, and a systematic review was conducted to evaluate whether preoperative MRI findings could predict shunt response. RESULTS: Postoperative complications within one month after surgery were observed in 6.8% (13/192), and the most common complication was hemorrhage. Changes in corpus callosum were observed in 4.2% (8/192). The shunt-response rates were 83.5% (106/127) in the 1-month follow-up group and 70.1% (54/77) in 1-year follow-up group. In the logistic regression analysis, only Evans' index measuring >0.4 had a significant negative relationship with shunt response at 1-month follow-up; however, no significant relationship was observed at 1-year follow-up. According to our systematic review, it is still controversial whether preoperative MRI findings could predict shunt response. CONCLUSION: Evans' index measure of >0.4 had a significant relationship with the shunt response in the 1-month follow-up group. In systematic reviews, there is ongoing debate about whether preoperative MRI findings can accurately predict responses to shunt surgery. Postoperative corpus callosal change was observed in 4.2% of iNPH patients.

Prospective evaluation of flow-regulated valves for idiopathic normal pressure hydrocephalus: 1-year results.

OBJECTIVE: Overdrainage and frequent reprogramming are common problems with programmable valves after ventriculoperitoneal shunt surgery for idiopathic normal pressure hydrocephalus (iNPH). Non-adjustable, flow-regulated valves offer a potential solution to these problems, but there is limited data on their efficacy. This study will evaluate neurological improvement and overdrainage rates within one year of treatment with a flow-regulated valve. PATIENTS AND METHODS: This prospective study analyzes 45 iNPH patients (median age: 73 years) treated with a flow-regulated valve. Clinical evaluations were performed at baseline, postoperatively, and at 3, 6, and 12 months after surgery. The primary efficacy endpoint was improvement of at least 5 points on the iNPH grading scale at follow-up. The safety endpoint was radiographic evidence of overdrainage. RESULTS: All patients presented with gait disturbance, 35 (78 %) had cognitive impairment, and 35 (78 %) had urinary incontinence. The median duration of symptoms was 24 months. The total iNPH score improved in 33/41 (81 %) at 3 months, in 29/34 (85 %) at 6 months, and in 22/29 (64 %) at 12 months. Overall, 40/45 (89 %) patients had a significant improvement on the iNPH scale. Secondary worsening of symptoms after initial improvement was observed in 5 (11 %) patients. Overdrainage occurred in one patient (2 %) requiring surgical evacuation. CONCLUSION: Treatment of iNPH patients with flow-regulated valves resulted in a good neurological outcome with minimal rates of overdrainage. These results are encouraging and justify the clinical use of these valve types.

Symptoms and signs did not predict outcome after surgery: a prospective study of 143 patients with idiopathic normal pressure hydrocephalus.

OBJECTIVE: To determine the utility of symptoms, signs, comorbidities and background variables for the prediction of outcome of treatment in iNPH. METHODS: A prospective observational study of consecutively included iNPH patients, who underwent neurological, physiotherapeutic and neuropsychological assessments before and after shunt surgery. The primary outcome measure was the total change on the iNPH scale, and patients were defined as improved postoperatively if they had improved by at least five points on that scale. RESULTS: 143 iNPH patients were included, and 73% of those were improved after surgery. None of the examined symptoms or signs could predict which patients would improve after shunt surgery. A dominant subjective complaint of memory problems at baseline was predictive of non-improvement. The reported comorbidities, duration of symptoms and BMI were the same in improved and non-improved patients. Each of the symptom domains (gait, neuropsychology, balance, and continence) as well as the total iNPH scale score improved significantly (from median 53 to 69, p < 0.001). The proportions of patients with shuffling gait, broad-based gait, paratonic rigidity and retropulsion all decreased significantly. DISCUSSION: This study confirms that the recorded clinical signs, symptoms, and impairments in the adopted clinical tests are characteristic findings in iNPH, based on that most of them improved after shunt surgery. However, our clinical data did not enable predictions of whether patients would respond to shunt surgery, indicating that the phenotype is unrelated to the reversibility of the iNPH state and should mainly support diagnosis. Absence of specific signs should not be used to exclude patients from treatment.

Freezing of gait in idiopathic normal pressure hydrocephalus.

BACKGROUND: Reports of freezing of gait (FoG) in idiopathic normal pressure hydrocephalus (iNPH) are few and results are variable. This study's objective was to evaluate the frequency of FoG in a large cohort of iNPH patients, identify FoG-associated factors, and assess FoG's responsiveness to shunt surgery. METHODS: Videotaped standardized gait protocols with iNPH patients pre- and post-shunt surgery (n = 139; median age 75 (71-79) years; 48 women) were evaluated for FoG episodes by two observers (Cohens kappa = 0.9, p < 0.001). FoG episodes were categorized. Mini-mental state examination (MMSE) and MRI white matter hyperintensities (WMH) assessment using the Fazekas scale were performed. CSF was analyzed for Beta-amyloid, Tau, and Phospho-tau. Patients with and without FoG were compared. RESULTS: Twenty-two patients (16%) displayed FoG at baseline, decreasing to seven (8%) after CSF shunt surgery (p = 0.039). The symptom was most frequently exhibited during turning (n = 16, 73%). Patients displaying FoG were older (77.5 vs. 74.6 years; p = 0.029), had a slower walking speed (0.59 vs. 0.89 m/s; p < 0.001), a lower Tinetti POMA score (6.8 vs. 10.8; p < 0.001), lower MMSE score (21.3 vs. 24.0; p = 0.031), and longer disease duration (4.2 vs. 2.3 years; p < 0.001) compared to patients not displaying FoG. WMH or CSF biomarkers did not differ between the groups. CONCLUSIONS: FoG is occurring frequently in iNPH patients and may be considered a typical feature of iNPH. FoG in iNPH was associated with higher age, longer disease duration, worse cognitive function, and a more unstable gait. Shunt surgery seems to improve the symptom.

Comparing the Long-Term Cardiovascular Outcomes of Lumbo-Peritoneal, Ventriculo-Peritoneal, or Non-Shunting Treatment after Idiopathic Normal Pressure Hydrocephalus: A Nationwide Retrospective Cohort Study.

Purpose: With advances in medical technology, the average lifespan has increased, leading to a growing significance of idiopathic normal pressure hydrocephalus (iNPH), particularly in the elderly population. Most patients with iNPH have been treated either with ventriculo-peritoneal shunts (VPS) or conservative measures. However, lumbo-peritoneal shunts (LPS) have emerged as an alternative treatment option for iNPH in recent decades, extensive research still lacks comparing outcomes with LPS to those with VPS or non-surgical treatment. The aim of the resent study is to disclose the long-term therapeutic outcomes of LPS, VPS, and non-shunting in patients with iNPH. Methods: We used the National Health Insurance Research Database in Taiwan to assess the long-term outcomes of these treatment options. We enrolled 5,537 iNPH patients who received shunting surgery, of which 5,254 were VPS and 283 were LPS. To compare the difference between each group, matching was conducted by propensity score matching using a 1:1 ratio based on LPS patients. Primary outcomes included death and major adverse cardiovascular events (MACEs) Results: Our findings show that VPS resulted in significantly more MACEs than non-surgical treatment (Odds ratio: 1.83, 95% confidence interval: 1.16-2.90). In addition, both VPS and LPS groups had significantly lower overall mortality rates than non-shunting group. Moreover, LPS had lower overall mortality but similar MACEs rates to VPS. Conclusions: Based on these findings, we propose that the LPS is preferable to the VPS, and surgical treatment should be considered the primary choice over conservative treatment unless contraindications are present.