Use of cortical volume to predict response to temporary CSF drainage in patients with idiopathic normal pressure hydrocephalus

J Neurosurg 139:1776–1783, 2023

Temporary drainage of CSF with lumbar puncture or lumbar drainage has a high predictive value for identifying patients with suspected idiopathic normal pressure hydrocephalus (iNPH) who may benefit from ventriculoperitoneal shunt insertion. However, it is unclear what differentiates responders from nonresponders. The authors hypothesized that nonresponders to temporary CSF drainage would have patterns of reduced regional gray matter volume (GMV) as compared with those of responders. The objective of the current investigation was to compare regional GMV between temporary CSF drainage responders and nonresponders. Machine learning using extracted GMV was then used to predict outcomes.

METHODS This retrospective cohort study included 132 patients with iNPH who underwent temporary CSF drainage and structural MRI. Demographic and clinical variables were examined between groups. Voxel-based morphometry was used to calculate GMV across the brain. Group differences in regional GMV were assessed and correlated with change in results on the Montreal Cognitive Assessment (MoCA) and gait velocity. A support vector machine (SVM) model that used extracted GMV values and was validated with leave-one-out cross-validation was used to predict clinical outcome.

RESULTS There were 87 responders and 45 nonresponders. There were no group differences in terms of age, sex, baseline MoCA score, Evans index, presence of disproportionately enlarged subarachnoid space hydrocephalus, baseline total CSF volume, or baseline white matter T2-weighted hyperintensity volume (p > 0.05). Nonresponders demonstrated decreased GMV in the right supplementary motor area (SMA) and right posterior parietal cortex as compared with responders (p < 0.001, p < 0.05 with false discovery rate cluster correction). GMV in the posterior parietal cortex was associated with change in MoCA (r 2 = 0.075, p < 0.05) and gait velocity (r 2 = 0.076, p < 0.05). Response status was classified by the SVM with 75.8% accuracy.

CONCLUSIONS Decreased GMV in the SMA and posterior parietal cortex may help identify patients with iNPH who are unlikely to benefit from temporary CSF drainage. These patients may have limited capacity for recovery due to atrophy in these regions that are known to be important for motor and cognitive integration. This study represents an important step toward improving patient selection and predicting clinical outcomes in the treatment of iNPH.

The benefits of automated CSF drainage in normal pressure hydrocephalus

Acta Neurochirurgica (2023) 165:1505–1509

The commonly used cerebrospinal fluid (CSF) drainage system remains the manual drip-chamber drain. The LiquoGuard (Möller Medical GmbH, Germany) is an automated CSF management device with dual functionality, measuring intracranial pressure and automatic pressure- or volume-led CSF drainage. There is limited research for comparison of devices, particularly in the neurosurgical field, where it has potential to reshape care.

Objective This study aims to compare manual drip-chamber drain versus LiquoGuard system, by assessing accuracy of drainage, associated morbidity and impact on length of stay.

Method Inclusion criteria consisted of suspected normal pressure hydrocephalus (NPH) patients undergoing extended lumbar drainage. Patients were divided into manual drain group versus automated group.

Results Data was analysed from 42 patients: 31 in the manual group versus 11 in the LiquoGuard group. Volumetric overdrainage was seen in 90.3% (n = 28) versus 0% (p < 0.05), and under-drainage in 38.7% (n = 12) versus 0% (p < 0.05), in the manual and automatic group, respectively. Symptoms of over-drainage were noted in 54.8% (n = 17) of the manual group, all of which had episodes of volumetric over-drainage, versus 18.2% (n = 2) in automated group, of which neither had actual over-drainage (p < 0.05). Higher over-drainage symptoms of manual drain is likely due to increased fluctuation of CSF drainage, instead of smooth CSF drainage seen with LiquoGuard system. An increased length of stay was seen in 38.7% (n = 12) versus 9% (n = 1) (p < 0.05) in the manual and LiquoGuard group, respectively.

Conclusion The LiquoGuard device is a more superior way of CSF drainage in suspected NPH patients, with reduced morbidity and length of stay.

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.

Prediction of Shunt Responsiveness in Suspected Patients With Normal Pressure Hydrocephalus Using the Lumbar Infusion Test: A Machine Learning Approach

Neurosurgery 90:407–418, 2022

Machine learning (ML) approaches can significantly improve the classical Rout -based evaluation of the lumbar infusion test (LIT) and the clinical management of the normal pressure hydrocephalus.

OBJECTIVE: To develop a ML model that accurately identifies patients as candidates for permanent cerebral spinal fluid shunt implantation using only intracranial pressure and electrocardiogram signals recorded throughout LIT.

METHODS: This was a single-center cohort study of prospectively collected data of 96 patients who underwent LIT and 5-day external lumbar cerebral spinal fluid drainage (external lumbar drainage) as a reference diagnostic method. A set of selected 48 intracranial pressure/ electrocardiogram complex signal waveform features describing nonlinear behavior, wavelet transform spectral signatures, or recurrent map patterns were calculated for each patient. After applying a leave-one-out cross-validation training–testing split of the data set, we trained and evaluated the performance of various state-of-the-art ML algorithms.

RESULTS: The highest performing ML algorithm was the eXtreme Gradient Boosting. This model showed a good calibration and discrimination on the testing data, with an area under the receiver operating characteristic curve of 0.891 (accuracy: 82.3%, sensitivity: 86.1%, and specificity: 73.9%) obtained for 8 selected features. Our ML model clearly outperforms the classical Rout based manual classification commonly used in clinical practice with an accuracy of 62.5%.

CONCLUSION: This study successfully used the ML approach to predict the outcome of a 5-day external lumbar drainage and hence which patients are likely to benefit from permanent shunt implantation. Our automated ML model thus enhances the diagnostic utility ofLIT in management.

Clinical significance of vitamin D in idiopathic normal pressure hydrocephalus

Acta Neurochirurgica (2021) 163:1969–1977

Although recent studies show vitamin D deficiency is associated with cognitive decline, urinary incontinence, and gait instability, there has been no study on the effect of vitamin D on idiopathic normal pressure hydrocephalus (iNPH) characterized by the classic symptom triad of cognitive decline, urinary incontinence, and gait instability. We investigated the clinical significance of vitamin D in patients with iNPH.

Methods Between 2017 and 2020, 44 patients who underwent ventriculoperitoneal shunt surgery were divided into low (< 15 ng/mL) and high (≥ 15 ng/mL) vitamin D groups according to the concentration of 25(OH)D, an effective indicator of vitamin D status. They were respectively evaluated according to clinical and radiological findings.

Results The low vitamin D group (n = 24) showed lower preoperative cognition compared to the high vitamin D group (n = 20) in terms of Korean-Mini Mental Status Examination (K-MMSE) and iNPH grading scale (iNPHGS) (K-MMSE: 20.5   5.4 versus 24.0   4.5, p = 0.041; iNPHGS cognitive score: 2   0.9 versus 1   0.6, p = 0.025). And the low vitamin D group showed pre- and postoperatively more severe urinary incontinence (preoperative iNPHGS urinary score: 1   1.0 versus 0   0.9, p = 0.012; postoperative iNPHGS urinary score:1   1.0 versus 0   0.9, p = 0.014). The score of narrow high-convexity sulci for the low vitamin D group was lower (low vitamin D group: 1   0.7 versus high vitamin D group: 2   0.4, p = 0.031).

Conclusion Lower concentration of vitamin D in iNPH may be related to lower preoperative cognition, pre- and postoperative urinary incontinence, and brain morphological change.

Ultra-low-pressure hydrocephalic state in NPH: benefits of therapeutic siphoning with adjustable antigravity valves

Acta Neurochirurgica (2020) 162:2967–2974

Idiopathic normal-pressure hydrocephalus (NPH) is a condition of the elderly treated by ventriculoperitoneal shunt (VP) insertion. A subset of NPH patients respond only temporarily to shunt insertion despite low valve opening pressure. This study aims to describe our experience of patients who benefit from further CSF drainage by adding adjustable antigravity valves and draining CSF at ultra-low pressure.

Methods Single-centre retrospective case series of patients undergoing shunt valve revision from an adjustable differential pressure valve with fixed antigravity unit to a system incorporating an adjustable gravitational valve (Miethke proSA). Patients were screened from a database of NPH patients undergoing CSF diversion over 10 consecutive years (April 2008– April 2018). Clinical records were retrospectively reviewed for interventions and clinical outcomes.

Results Nineteen (10F:9M) patients underwent elective VP shunt revision to a system incorporating an adjustable gravitational valve. Mean age 77.1 ± 7.1 years (mean ± SD). Eleven patients (58%) showed significant improvement in walking speed following shunt revision. Fourteen patients/carers (74%) reported subjective improvements in symptoms following shunt revision.

Conclusions Patients presenting symptoms relapse following VP shunting may represent a group of patients with ultra-low pressure hydrocephalus, for whom further CSF drainage may lead to an improvement in symptoms. These cases may benefit from shunt revision with an adjustable gravitational valve, adjustment of which can lead to controlled siphoning of CSF and drain CSF despite ultra-low CSF pressure.

Risk factors, comorbidities, quality of life, and complications after surgery in idiopathic normal pressure hydrocephalus: review of the INPH-CRasH study

Neurosurg Focus 49 (4):E8, 2020

Idiopathic normal pressure hydrocephalus (INPH) is a dementia treatable by insertion of a shunt that drains CSF. The cause of the disease is unknown, but a vascular pathway has been suggested. The INPH-CRasH (Comorbidities and Risk Factors Associated with Hydrocephalus) study was a modern epidemiological case-control study designed to prospectively assess parameters regarding comorbidities and vascular risk factors (VRFs) for INPH, quality of life (QOL), and adverse events in patients with shunted INPH. The objective of this review was to summarize the findings of the INPH-CRasH study.

METHODS VRFs, comorbidities, QOL, and adverse events were analyzed in consecutive patients with INPH who underwent shunt placement between 2008 and 2010 in 5 of 6 neurosurgical centers in Sweden. Patients (n = 176, within the age span of 60–85 years and not having dementia) were compared to population-based age- and gender-matched controls (n = 368, same inclusion criteria as for the patients with INPH). Assessed parameters were as follows: hypertension; diabetes; obesity; hyperlipidemia; psychosocial factors (stress and depression); smoking status; alcohol intake; physical activity; dietary pattern; cerebrovascular, cardiovascular, or peripheral vascular disease; epilepsy; abdominal pain; headache; and clinical parameters before and after surgery. Parameters were assessed through questionnaires, clinical examinations, measurements, ECG studies, and blood samples.

RESULTS Four VRFs were independently associated with INPH: hyperlipidemia, diabetes, obesity, and psychosocial factors. Physical inactivity and hypertension were also associated with INPH, although not independently from the other risk factors. The population attributable risk percent for a model containing all of the VRFs associated with INPH was 24%. Depression was overrepresented in patients with INPH treated with shunts compared to the controls (46% vs 13%, p < 0.001) and the main predictor for low QOL was a coexisting depression (p < 0.001). Shunting improved QOL on a long-term basis. Epilepsy, headache, and abdominal pain remained common for a mean follow-up time of 21 months in INPH patients who received shunts.

CONCLUSIONS The results of the INPH-CRasH study are consistent with a vascular pathophysiological component of INPH. In clinical care and research, a complete risk factor analysis as well as screening for depression and a measurement for QOL should probably be included in the workup of patients with INPH. The effect of targeted interventions against modifiable VRFs and antidepressant treatment in INPH patients should be evaluated. Seizures, headache, and abdominal pain should be inquired about at postoperative follow-up examinations.

Effect of fixed-setting versus programmable valve on incidence of shunt revision after ventricular shunting for idiopathic normal pressure hydrocephalus

J Neurosurg 133:564–572, 2020

Although ventricular shunting is an effective therapy for idiopathic normal pressure hydrocephalus (iNPH), the effect of shunt valve type on the incidence of revision surgery is not well defined. To address this issue, shunt revision rates between patients with iNPH receiving a fixed-setting valve (FSV) versus a programmable valve (PV) were compared.

METHODS Patients with iNPH treated with ventricular shunting between 2001 and 2017 were included for analysis. The incidence of shunt revision was noted and risk factors for revision were identified using a Cox proportional hazards model. Costs associated with admission for ventricular shunt procedures were obtained from the Vizient national database.

RESULTS There were 348 patients included for analysis, with 98 patients (28.1%) receiving a PV. Shunt revision occurred in 73 patients (21.0%), with 12 patients (3.4%) undergoing multiple revisions. Overall revision rates were lower in patients receiving a PV (13.3% vs 24.0%; p = 0.027), as was the incidence of multiple revisions (0.0% vs 4.8%; p = 0.023). Patients with initial placement of an FSV were also more likely to undergo valve exchange during follow-up (12.4% vs 2.0%; p = 0.003). Patients with a PV were less likely to undergo revision due to persistent symptoms without obstruction (2.0% vs 8.8%; p = 0.031) and distal obstruction (1.0% vs 6.8%; p = 0.030). In a multivariate Cox proportional hazards model, initial placement of a PV was associated with reduced risk of revision due to persistent symptoms without obstruction (OR 0.27, 95% CI 0.04–0.93; p = 0.036). PVs were associated with more frequent shunt series (1.3 vs 0.6; p < 0.001) and head CT scans (3.6 vs 2.7; p = 0.038) during follow-up. There was no significant difference in mean total costs between patients receiving an FSV and a PV ($24,282.50 vs $24,396.90; p = 0.937).

CONCLUSIONS The authors’ results suggest that PVs lead to reduced rates of shunt revision in patients with iNPH, and decreased risk of revision due to persistent symptoms of iNPH, thereby justifying the higher upfront cost of PVs despite similar overall treatment costs between these devices.


Clinical outcomes of normal pressure hydrocephalus in 116 patients: objective versus subjective assessment

J Neurosurg 132:1757–1763, 2020

Objective assessment tests are commonly used to predict the response to ventriculoperitoneal (VP) shunting in patients with normal pressure hydrocephalus (NPH). Whether subjective reports of improvement after a lumbar drain (LD) trial can predict response to VP shunting remains controversial. The goal in this study was to compare clinical characteristics, complication rates, and shunt outcomes of objective and subjective LD responders who underwent VP shunt placement.

METHODS This was a retrospective review of patients with NPH who underwent VP shunt placement after clinical improvement with the LD trial. Patients who responded after the LD trial were subclassified into objective LD responders and subjective LD responders. Clinical characteristics, complication rates, and shunt outcomes between the 2 groups were compared with chi-square test of independence and t-test.

RESULTS A total of 116 patients received a VP shunt; 75 were objective LD responders and 41 were subjective LD responders. There was no statistically significant difference in patient characteristics between the 2 groups, except for a shorter length of stay after LD trial seen with subjective responders. The complication rates after LD trial and VP shunting were not significantly different between the 2 groups. Similarly, there was no significant difference in shunt response between objective and subjective LD responders. The mean duration of follow-up was 1.73 years.

CONCLUSIONS Reports of subjective improvement after LD trial in patients with NPH can be a reliable predictor of shunt response. The currently used objective assessment scales may not be sensitive enough to detect subtle changes in symptomatology after LD trial.

Thirty-Day Hospital Readmission and Surgical Complication Rates for Shunting in Normal Pressure Hydrocephalus: A Large National Database Analysis

Neurosurgery 86:843–850, 2020

Research on age-related complications secondary to shunts in normal pressure hydrocephalus (NPH) is primarily limited to single-center studies and small cohorts.

OBJECTIVE: To determine the rates of hospital readmission and surgical complications, and factors that predict them, following shunt surgery for NPH in a large healthcare network.

METHODS: Surgical procedures, complications, and readmissions for adults undergoing ventricular shunting for NPH were determined using de-identified claims from a privately insured United States healthcare network in years 2007-2014. Univariate and multivariate statistics were used to determine factors that predict poor surgical outcomes. The primary outcome variable was surgical complications or readmissions (composite variable for any major perioperative complication or 30-d readmission).

RESULTS: The 30-d readmission rate for 974 patients with NPH who underwent ventricular shunting was 7.29%; the most common reasons for readmission were shunt-related complications, infection, hemorrhage, altered mental status, and cardiopulmonary and musculoskeletal problems. The perioperative complication rate was 21.15%, including intraparenchymal hemorrhage (5.85%) and extra-axial (subdural or epidural) hematoma (5.54%). The overall rate of having a surgical complication or 30-d readmission was 25.15%. Age did not predict surgical complication or 30-d readmission. Preoperative comorbidities independently associated with poor outcome were myocardial infarction within 1 yr (OR = 3.984, 95% CI = 1.105-14.368); existing cerebrovascular disease (odds ratio [OR] = 2.206, 95% CI = 1.544-3.152); and moderate/severe renal disease (OR = 2.000, 95% CI = 1.155-3.464).

CONCLUSION: The rate of complications or readmission within 30 d of ventricular shunting for NPH is 25.15%. Preoperative comorbidities of myocardial infarction within 1 yr, cerebrovascular disease, and moderate/severe renal disease are independent risk factors for poor outcome.

Timing of intraventricular infusion test for diagnosing idiopathic normal pressure hydrocephalus

Acta Neurochirurgica (2020) 162: 1011–1017

Infusion tests, which measure resistance to outflow (Rout), are used in selecting patients suspected for idiopathic normal pressure hydrocephalus (iNPH) for shunt surgery. Infusion tests can be performed through an external ventricular drain (EVD). A 24-hour time gap from EVD insertion to an infusion test is a routine practice at our department due to concerns that the surgical procedure might influence the test results in the immediate postoperative period. The objective of the study was to investigate if timing of an intraventricular infusion test influences the results of the test in patients suspected for iNPH.

Methods Ten patients scheduled for an intraventricular infusion test were included. Measurements of baseline intracranial pressure (ICP) and plateau ICP were obtained during constant rate intraventricular infusion test performed at two time points (1 and 24 h after EVD insertion) and Rout was calculated from these measures and compared within patients.

Results Eight patients completed both infusion tests. In one of the 18 infusion tests performed, it was not possible to define an ICP plateau and this infusion test was excluded, leaving 7 paired infusion tests.Median Rout was 12.9 mmHg/ml/min (range 7.0–22.0) 1 h after EVD insertion and 11.3 mmHg/ml/min (range 7.8–18.1) after 24 h. Overall, there were no statistically significant differences in Rout (P = 0.83), baseline ICP (P = 0.70), or plateau ICP (P = 0.81) between the recordings performed 1 h and 24 h after EVD insertion. For two of the seven patients with paired infusion tests, there was poor agreement between Rout values at 1 and 24 h.

Conclusion Overall, Rout estimates do not change significantly between 1 and 24 h after EVD insertion.We therefore propose that infusion tests can be performed shortly after surgery to reduce the period of indwelling EVD and duration of hospitalization.

Lumbar drain trial outcomes of normal pressure hydrocephalus: a single-center experience of 254 patients

J Neurosurg 132:306–312, 2020

A short-term lumbar drain (LD) trial is commonly used to assess the response of normal pressure hydrocephalus (NPH) patients to CSF diversion. However, it remains unknown whether the predictors of passing an LD trial match the predictors of improvement after ventriculoperitoneal shunting. The aim of this study was to examine outcomes, complication rates, and associations between predictors and outcomes after an LD trial in patients with NPH.

METHODS The authors retrospectively reviewed the records of 254 patients with probable NPH who underwent an LD trial between March 2008 and September 2017. Multivariate regression models were constructed to examine predictors of passing the LD trial. Complications associated with the LD trial procedure were recorded.

RESULTS The mean patient age was 77 years and 56.7% were male. The mean durations of gait disturbance, cognitive decline, and urinary incontinence were 29 months, 32 months, and 28 months, respectively. Of the 254 patients, 30% and 16% reported objective and subjective improvement after the LD trial, respectively. Complications included a sheared LD catheter, meningitis, lumbar epidural abscess, CSF leak at insertion site, transient lower extremity numbness, slurred speech, refractory headaches, and hyponatremia. Multivariate analyses using MAX-R revealed that a prior history of stroke predicted worse outcomes, while disproportionate subarachnoid spaces (uneven enlargement of supratentorial spaces) predicted better outcomes after the LD trial (r2 = 0.12, p < 0.05).

CONCLUSIONS The LD trial is generally safe and well tolerated. The best predictors of passing the LD trial include a negative history of stroke and having disproportionate subarachnoid spaces.


Ventriculoperitoneal shunt in treating of idiopathic normal pressure hydrocephalus—single-center study

Acta Neurochirurgica (2020) 162:1–7

Idiopathic normal pressure hydrocephalus (iNPH) is the only variant of dementia disorders possibly treatable by neurosurgical intervention. iNPH is a neurodegenerative condition clinically characterized by gait ataxia, urinary incontinence, and memory disturbance. We present one of the largest single-center studies, which was designed to prove efficacy of our low-pressure setting of gravitational valve at all three symptoms of iNPH and to find statistically significant cut-off time for best clinical improvement according to the duration of symptoms.

Methods Sixty-one consecutive patients (mean age 74.9 ± 5.3) with iNPH were prospectively observed from the time of surgery with minimal 6 months follow-up. All patients underwent implantation of the same type of gravitational valve with the same setting—pro GAV with low opening pressure at 5 cm H2O—and were operated by the same team of 2 neurosurgeons. We statistically evaluated gait disturbance, psychological changes, and incontinence preoperatively and at 6 months after surgery and timing of the surgery according to the duration of symptoms and to the age.

Results Paired t test showed a statistically significant increase in MMSE, a statistically significant decrease in 10-m walk test and 360 deg. rotation test (p < 0.0001). The correlation among the change of the MMSE, the walk test, and the rotation test, and the age and time of symptoms’ duration was verified by Pearson’s correlation coefficient. Pearson’s correlation coefficient showed a medium strong correlation between the change of MMSE and the time of symptoms (r = − 0.580; p < 0.0001) and between the change of the number of steps and the time of symptoms (r = 0.517, p < 0.0001). There was a statistically significant weak (poor) correlation between the change of the walk test and the time of symptoms (r = 0.351, p = 0.006). All 3 ROC tests confirmed optimal cut-off for the best improvement of symptoms as 9.5 months of the symptom duration.

Conclusions We proved statistical significant optimal cut-off for the best improvement of the symptoms as 9.5 months of the symptom duration. This study also confirmed successful treatment of iNPH with VP shunting using low pressure setting of gravitational valve with overall improvement in 75% and low over drainage complications in 5%. We proved statistically significant increase in MMSE, decrease in 10 m walk test and number of steps test, p < 0.0001.

Comparison of the CSF dynamics between patients with idiopathic normal pressure hydrocephalus and healthy volunteers

J Neurosurg 131:1018–1023, 2019

Intracranial pressure (ICP), outflow resistance (R out ), and amplitude of cardiac-related ICP pulsations (AMPs) are established parameters to describe the CSF hydrodynamic system and are assumed, but not confirmed, to be disturbed in idiopathic normal pressure hydrocephalus (INPH). The aim of this study was to compare the CSF hydrodynamic profile between patients with INPH and healthy volunteers.

METHODS Sixty-two consecutive INPH patients (mean age 74 years) and 40 healthy volunteers (mean age 70 years) were included. Diagnosis was made by two independent neurologists who assessed patients’ history, neurological status, and MRI studies. A CSF dynamic investigation through the lumbar route was performed: ICP and other CSF dynamic variables were blinded to the neurologists during the diagnostic process and were not used for establishing the diagnosis of INPH.

RESULTS R out was significantly higher in INPH (R out 17.1 vs 11.1; p < 0.001), though a substantial number of INPH subjects had normal R out . There were no differences between INPH patients and controls regarding ICP (mean 11.5 mm Hg). At resting pressure, there was a trend that AMP in INPH was increased (2.4 vs 2.0 mm Hg; p = 0.109). The relationship between AMP and ICP was that they shared the same slope, but the curve was significantly shifted to the left for INPH (reduced P 0 [p < 0.05]; i.e., higher AMP for the same ICP).

CONCLUSIONS This study established that the CSF dynamic profile of INPH deviates from that of healthy volunteers and that INPH should thus be regarded as a disease in which intracranial hydrodynamics are part of the pathophysiology.

Clinical trial registration no.: NCT01188382 (

Idiopathic Normal-Pressure Hydrocephalus: Diagnostic Accuracy of Automated Sulcal Morphometry in Patients With Ventriculomegaly

Neurosurgery 85:E747–E755, 2019

Idiopathic normal-pressure hydrocephalus (iNPH) is a treatable cause of gait and cognitive impairment. iNPH should be differentiated from ventriculomegaly secondary to brain atrophy to choose the best therapeutic option (ventriculoperitoneal shunt vs medical management).

OBJECTIVE: To determine the diagnostic accuracy of automated sulcal morphometry to differentiate patients with iNPH from patients with ventriculomegaly of neurodegenerative origin.

METHODS: Thirty-eight consecutive patients with iNPH (shunt responsive n = 31, nonresponsive n = 7), 35 with vascular cognitive disorder, and 25 age- and sex-matched healthy controls were prospectively included and underwent cognitive evaluation and 3T brain magnetic resonance imaging. Sulcal opening of 10 sulci of interest was retrospectively measured using an automated surface-based approach from the 3-dimensional T1-weighted images. Receiver-operating characteristic curve analyses determined the best parameter to identify iNPH patients.

RESULTS: The best parameter to discriminate shunt-responsive iNPH from patients with vascular cognitive disorder and healthy controls was the ratio between calcarine sulcus and cingulate sulcus opening with an area under the curve of 0.94 (95% CI: 0.89, 0.99). A cut-off value of 0.95 provided the highest sensitivity (96.8%) and specificity (83.3%).

CONCLUSION: This preliminary study showed that automated sulcal morphometry may help the neurosurgeon to identify iNPH patients and to exclude other causes of ventriculomegaly.


Prevalence of Schizophrenia in Idiopathic Normal Pressure Hydrocephalus

Neurosurgery 84:883–889, 2019

Idiopathic normal pressure hydrocephalus (iNPH) is a progressive and potentially treatable neurodegenerative disease affecting elderly people, characterized by gait impairment and ventricular enlargement in brain imaging. Similar findings are seen in some patients with schizophrenia (SCZ).

OBJECTIVE: To determine the prevalence of SCZ among patients suffering from probable or possible iNPH and the specific effects of comorbid SCZ on the outcome of the cerebrospinal fluid (CSF) shunting.

METHODS: All medical records of the 521 iNPH patients in the NPH registry were retrospectively analyzed from 1991 until 2017. The prevalence of comorbidity of SCZ was determined and compared to that of general aged (≥65 yr) population in Finland.

RESULTS: We identified a total of 16 (3.1%) iNPH patients suffering from comorbid SCZ. The prevalence of SCZ among the iNPH patients was significantly higher compared to the general population (3.1% vs 0.9%, P < .001). All iNPH patients with comorbid SCZ were CSF shunted and 12 (75%) had a clinically verified shunt response 3 to 12mo after the procedure. The CSF shunt response rate did not differ between patients with and without comorbid SCZ.

CONCLUSION: SCZ seems to occur 3 times more frequently among iNPH patients compared to the general aged population in Finland. The outcome of the treatment was not affected by comorbid SCZ and therefore iNPH patients suffering from comorbid SCZ should not be left untreated. These results merit validation in other populations. In addition, further research towards the potential connection between these chronic conditions is warranted.

Glaucoma in patients with shunt-treated normal pressure hydrocephalus

J Neurosurg 129:1078–1084, 2018

Changes in the pressure gradient between intraocular and intracranial compartments at the lamina cribrosa level are a possible explanation of normal tension glaucoma (NTG). Shunt-treated normal pressure hydrocephalus (NPH) is a model for testing whether the increase (time from disease onset to CSF shunt placement, i.e., “protection period”) and decrease (time from shunt placement to observation, i.e., “exposure period”) in intracranial pressure (ICP) are glaucoma protective or risk factors, respectively. The authors estimated the prevalence of NTG in patients with shunt-treated NPH and calculated the extent of optic nerve exposure to changes in the trans–lamina cribosa gradient.

METHODS Data obtained in patients with NPH who had undergone ventriculoperitoneal (VP) shunt placement were analyzed. Patients with more than 6 months’ follow-up, no pathologies associated with ICP changes or CSF dynamics disturbances, and no surgical or valve-related complications were scheduled for ophthalmic evaluation.

RESULTS Nine of 22 patients had NTG, which is about a 40-fold increase in rate compared with the rate in the general elderly population without hydrocephalus (p < 0.001). The median protection period was 12.0 months in patients with NTG and 18.0 months in those without NTG (p = 0.033). The median ICP decrease multiplied by duration of exposure in months was 76.0 mm Hg × months in the NTG group and 24.1 mm Hg × months in the no-NTG group (p = 0.048). The patients’ median adjusted age (adjusted for “protection” and “exposure” times) was 85.1 years in the NTG group and 78.8 years in the no-NTG group (p = 0.001).

CONCLUSIONS A crucial risk factor for development of NTG in patients with shunt-treated NPH is the duration of optic nerve exposure to the lowering of ICP. Patients with NPH who are candidates for CSF shunting should be informed of the risk of incurring glaucoma. Longitudinal studies could provide estimates of tolerated times for a given ICP decrease.

Association between shunt-responsive idiopathic normal pressure hydrocephalus and alcohol

J Neurosurg 127:240–248, 2017

Idiopathic normal pressure hydrocephalus (iNPH) is characterized by ventriculomegaly, gait difficulty, incontinence, and dementia. The symptoms can be ameliorated by CSF drainage. The object of this study was to identify factors associated with shunt-responsive iNPH.

METHODS The authors reviewed the medical records of 529 patients who underwent shunt placement for iNPH at their institution between July 2001 and March 2015. Variables associated with shunt-responsive iNPH were identified using bivariate and multivariate analyses. Detailed alcohol consumption information was obtained for 328 patients and was used to examine the relationship between alcohol and shunt-responsive iNPH. A computerized patient registry from 2 academic medical centers was queried to determine the prevalence of alcohol abuse among 1665 iNPH patients.

RESULTS Bivariate analysis identified associations between shunt-responsive iNPH and gait difficulty (OR 4.59, 95% CI 2.32–9.09; p < 0.0001), dementia (OR 1.79, 95% CI 1.14–2.80; p = 0.01), incontinence (OR 1.77, 95% CI 1.13–2.76; p = 0.01), and alcohol use (OR 1.98, 95% CI 1.23–3.16; p = 0.03). Borderline significance was observed for hyperlipidemia (OR 1.56, 95% CI 0.99–2.45; p = 0.054), a family history of hyperlipidemia (OR 3.09, 95% CI 0.93–10.26, p = 0.054), and diabetes (OR 1.83, 95% CI 0.96–3.51; p = 0.064). Multivariate analysis identified associations with gait difficulty (OR 3.98, 95% CI 1.81–8.77; p = 0.0006) and alcohol (OR 1.94, 95% CI 1.10–3.39; p = 0.04). Increased alcohol intake correlated with greater improvement after CSF drainage. Alcohol abuse was 2.5 times more prevalent among iNPH patients than matched controls.

CONCLUSIONS Alcohol consumption is associated with the development of shunt-responsive iNPH.


Shunting of the over 80s in normal pressure hydrocephalus

Acta Neurochir (2017) 159:987–994

Idiopathic normal pressure hydrocephalus is predominantly a disease of the elderly. By its nature, many of those who present to clinic are in advanced old age with multiple comorbidities. Majority of patients treated are younger than 80 years old. We present the clinical outcomes and complication rates of patients over the age of 80 years at the time of operation, during the past 11 years at a single institution.

Methods Retrospective analysis of clinical records of all patients over the age of 80 years, who presented to our institution between 2006 and 2016.

Results were analysed for co-morbidities, immediate and delayed complications, change in mobility/cognitive function post shunting of hydrocephalus.

Results 39 patients (24 male, 15 female) met criteria. Mean [SD] age at the time of shunt insertion was 84 years (+/− 3.22) (range 80–94). No patients developed immediate CSF infection or sub-dural collection, or extended length of stay due to surgical or anaesthetic complications. There were no perioperative or anaesthetic complications. 4 patients required a delayed surgical revision to encourage greater CSF drainage. 3 patients went on to develop delayed subdural haematoma, 1 of which was associated with trauma, 2 through overdrainage. 1 patient experienced poor post-operative wound healing and subsequently underwent removal of shunt. Of the 34 patient followed up, 27 patients (79.4%) improved in their mobility. (64.7%) patients/families reported symptomatic improvement in their cognition and memory. 6 (17.7%) patients did not experience an improvement in either mobility or cognitive function.

Conclusions Our data supports the assertion that, with proper patient selection, shunting of the over 80s with iNPH is a safe and effective procedure.

Walking assessment after lumbar puncture in normal-pressure hydrocephalus: a delayed improvement over 3 days

J Neurosur (126) 148-157, 2017

The determination of gait improvement after lumbar puncture (LP) in idiopathic normal-pressure hydrocephalus (iNPH) is crucial, but the best time for such an assessment is unclear. The authors determined the time course of improvement in walking after LP for single-task and dual-task walking in iNPH.

METHODS: In patients with iNPH, sequential recordings of gait velocity were obtained prior to LP (time point [TP]0), 1–8 hours after LP (TP1), 24 hours after LP (TP2), 48 hours after LP (TP3), and 72 hours after LP (TP4). Gait analysis was performed using a pressure-sensitive carpet (GAITRite) under 4 conditions: walking at preferred velocity (STPS), walking at maximal velocity (STMS), walking while performing serial 7 subtractions (dual-task walking with serial 7 [DTS7]), and walking while performing verbal fluency tasks (dual-task walking with verbal fluency [DTVF]).

RESULTS: Twenty-four patients with a mean age of 76.1 ± 7.8 years were included in this study. Objective responder status moderately coincided with the self-estimation of the patients with subjective high false-positive results (83%). The extent of improvement was greater for single-task walking than for dual-task walking (p < 0.05). Significant increases in walking speed were found at TP2 for STPS (p = 0.042) and DTVF (p = 0.046) and at TP3 for STPS (p = 0.035), DTS7 (p = 0.042), and DTVF (p = 0.044). Enlargement of the ventricles (Evans Index) positively correlated with early improvement. Gait improvement at TP3 correlated with the shunt response in 18 patients.

CONCLUSIONS: Quantitative gait assessment in iNPH is important due to the poor self-evaluation of the patients. The maximal increase in gait velocity can be observed 24–48 hours after the LP. This time point is also best to predict the response to shunting. For dual-task paradigms, maximal improvement appears to occur later (48 to 72 hours). Assessment of gait should be performed at Day 2 or 3 after LP.