OBJECTIVES:The aim of this study was to determine the prevalence of idiopathic normal-pressure hydrocephalus (iNPH) in elderly persons in a large population-based sample using radiologic and clinical ...examinations.
METHODS:We examined representative elderly populations aged 70 years and older that had undergone neuropsychiatric evaluations and CT of the brain between 1986 and 2000 (n = 1,238). Gait was evaluated by clinical examination and history of walking difficulty. Cognitive function was evaluated with the Mini-Mental State Examination and urinary incontinence by self-report. iNPH was diagnosed in concordance with the American-European iNPH guidelines. Exclusion criteria were history of meningitis, severe head trauma, and subarachnoid hemorrhage.
RESULTS:The prevalence of probable iNPH was 0.2% in those aged 70–79 years (n = 2) and 5.9% (n = 24) in those aged 80 years and older, with no difference between men and women. Only 2 of these persons had been treated for iNPH. Hydrocephalic ventricular enlargement, i.e., a CT image consistent with NPH, was found in 56 persons (4.5%). An Evans Index >0.3 was found in 256 (20.7%) and occluded sulci at the high convexity in 67 persons (5.4%). All of these findings were more common in the older age groups.
CONCLUSIONS:Many elderly possess clinical and imaging features of iNPH, especially those older than 80 years. The number of persons with iNPH is probably much higher than the number of persons currently treated.
Background and purpose
To 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.
Methods
In 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.
Results
Median 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).
Conclusions
The present data indicate that shunt surgery is effective in iNPH and that early treatment increases survival.
Patients with idiopathic normal pressure hydrocephalus exposed to 6–24 months delayed planning of shunt surgery had a more than twofold increased mortality compared to patients operated without delay.
This observational study aimed to explore the pathophysiology of idiopathic normal-pressure hydrocephalus (iNPH) and to evaluate the diagnostic and prognostic value of CSF biomarkers.
Lumbar CSF of ...patients with iNPH and healthy elderly individuals (HI) and ventricular CSF (VCSF) from the patients with iNPH pre and 6 months postsurgery were analyzed by ELISA. We analyzed neurofilament light protein (NFL), myelin basic protein (MBP), a panel of β-amyloid isoforms (Aβ38, Aβ40, and Aβ42), soluble amyloid precursor protein (sAPP) isoforms sAPPα and sAPPβ, total and phosphorylated tau protein (t- and p-tau), and inflammatory markers interleukin 8, interleukin 10, and monocyte chemoattractant protein 1.
NFL was elevated and amyloid precursor protein (APP)-derived proteins and tau proteins were lower in patients with iNPH than in HI. Postsurgery, there was an increase of NFL, APP-derived proteins, p-tau, and albumin in VCSF, whereas levels of MBP and t-tau had decreased. Improved patients showed a greater increase of APP-derived proteins in VCSF following shunting than did those who did not improve.
We interpret our data as iNPH pathophysiology to be characterized by a reduced periventricular metabolism and axonal degeneration but no major cortical damage.
IMPORTANCE: Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for ...neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date. OBJECTIVES: To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions. DATA SOURCES: PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC. STUDY SELECTION: Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex. DATA EXTRACTION AND SYNTHESIS: Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept. MAIN OUTCOME AND MEASURE: The cNfL levels adjusted for age and sex across diagnoses. RESULTS: Data were collected for 10 059 individuals (mean SD age, 59.7 18.8 years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes. CONCLUSIONS AND RELEVANCE: These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
Objectives The natural course of idiopathic normal pressure hydrocephalus (iNPH) has not been thoroughly studied. The consequences of postponing shunt treatment are largely unknown. We aimed to ...describe the effects of waiting for more than 6 months before surgery and to compare the outcome with that seen in patients who waited for less than 3 months. Methods 33 patients (iNPHDelayed) underwent an initial investigation (Pre-op 1), followed by re-examination, just prior to surgery, after waiting for at least 6 months (Pre-op 2). Outcome was evaluated after 3 months of treatment. 69 patients who were surgically treated within 3 months after Pre-op 1 and who were also evaluated after 3 months of treatment constituted a comparison group (iNPHEarly). Evaluations were done with the iNPH scale and the modified Rankin Scale (mRS). iNPHDelayed patients were prospectively studied with regard to outcome, whereas the comparison group iNPHEarly was defined and analysed retrospectively. Results iNPHDelayed patients deteriorated significantly during their wait for surgery, with progression of symptom severity ranging from +7 to −47 on the iNPH scale, and from 0 to +3 on the mRS (both p<0.001). The magnitude of change after surgery was similar in the groups, but since the symptoms of iNPHDelayed patients had worsened while waiting, their final outcome was significantly poorer. Conclusions The natural course of iNPH is symptom progression over time, with worsening in gait, balance and cognitive symptoms. This deterioration is only partially reversible. To maximise the benefits of shunt treatment, surgery should be performed soon after diagnosis.
Objective The objective was to determine the sensitivity, specificity, and positive and negative predictive values of the CSF Tap Test (CSF TT) and resistance to CSF outflow (Rout) for the outcome of ...shunting in a sample of patients with idiopathic normal pressure hydrocephalus (iNPH). Methods 115 patients were included in this European multicentre study. Diagnosis was based on clinical symptoms and signs, and MRI changes. All patients were treated with programmable ventriculoperitoneal shunts and re-examined 12 months after surgery. Outcomes were measures with a newly developed iNPH Scale and the modified Rankin Scale (mRS). Before surgery, a CSF TT and measurement of Rout was performed, with the results blinded to all caregivers. The 12 month outcome was correlated with Rout and the result of the CSF TT. Results Rout and the results of the CSF TT showed no correlation with outcome measured by either domain, or with total iNPH score or mRS score. Only an increase in the gait task (10 m of walking at free speed) of the CSF TT correlated significantly (r=0.22, p=0.02) with improvement in iNPH score. The positive predictive value of both tests was >90% and the negative predictive value <20%. Rout >12 had an overall accuracy of 65% and the CSF TT 53%. Combining both tests did not improve their predictive power. No correlation was found between Rout and the results of the CSF TT. Conclusions Rout and the results of the CSF TT did not correlate with outcome after 12 months. Rout and CSF TT can be used for selecting patients for shunt surgery but not for excluding patients from treatment. Trial registration The study has been registered at clinicaltrials.gov, identifier NCT00874198.
Objective
To describe survival and causes of death in 979 treated iNPH patients from the Swedish Hydrocephalus Quality Registry (SHQR), and to examine the influence of comorbidities, symptom severity ...and postoperative outcome.
Methods
All 979 patients operated for iNPH 2004–2011 and registered in the SHQR were included. A matched control group of 4890 persons from the general population was selected by Statistics Sweden. Data from the Swedish Cause of Death Registry was obtained for patients and controls.
Results
At a median 5.9 (IQR 4.2–8.1) year follow-up, 37% of the iNPH patients and 23% of the controls had died. Mortality was increased in iNPH patients by a hazard ratio of 1.81, 95% CI 1.61–2.04,
p
< 0.001. More pronounced symptoms in the preoperative ordinal gait scale and the Mini-mental State Examination were the most important independent predictors of mortality along with the prevalence of heart disease. Patients who improved in both the gait scale and in the modified Rankin Scale postoperatively (
n
= 144) had a similar survival as the general population (
p
= 0.391). Deaths due to cerebrovascular disease or dementia were more common in iNPH patients, while more controls died because of neoplasms or disorders of the circulatory system.
Conclusions
Mortality in operated iNPH patients is 1.8 times increased compared to the general population, a lower figure than previously reported. The survival of iNPH patients who improve in gait and functional independence is similar to that of the general population, indicating that shunt surgery for iNPH, besides improving symptoms and signs, can normalize survival.
OBJECTIVE:We examined clinical and imaging findings of suspected idiopathic normal pressure hydrocephalus (iNPH) in relation to vascular risk factors and white matter lesions (WMLs), using a nested ...case-control design in a representative, population-based sample.
METHODS:From a population-based sample, 1,235 persons aged 70 years or older were examined with CT of the brain between 1986 and 2000. We identified 55 persons with hydrocephalic ventricular enlargement, i.e., radiologic findings consistent with iNPH. Among these, 26 had clinical signs that fulfilled international guideline criteria for probable iNPH. These cases were labeled suspected iNPH. Each case was matched to 5 controls from the same sample, based on age, sex, and study cohort. Data on risk factors were obtained from clinical examinations and the Swedish Hospital Discharge Register. History of hypertension, diabetes mellitus (DM), smoking, overweight, history of coronary artery disease, stroke/TIA, and WMLs on CT were examined. Risk factors associated with iNPH with a p value <0.1 in χ tests were included in conditional logistic regression models.
RESULTS:In the regression analyses, suspected iNPH was related to moderate to severe WMLs (odds ratio OR 5.2; 95% confidence interval CI1.5–17.6), while hydrocephalic ventricular enlargement was related to hypertension (OR 2.7; 95% CI1.1–6.8), moderate to severe WMLs (OR 6.5; 95% CI2.1–20.3), and DM (OR 4.3; 95% CI1.1–16.3).
CONCLUSIONS:Hypertension, WMLs, and DM were related to clinical and imaging features of iNPH, suggesting that vascular mechanisms are involved in the pathophysiology. These findings might have implications for understanding disease mechanisms in iNPH and possibly prevention.
To investigate the prevalence of intracranial arachnoid cysts in a large population-based sample. We also aimed to assess the association between arachnoid cysts and cognitive impairment, depression, ...epilepsy, headache, dizziness, previous head trauma, hip fractures, and mortality. A population-based cohort and nested case–control study. The sample comprised representative populations (
n
= 1235) aged ≥70 years. All participants underwent baseline neuropsychiatric examinations, including computed tomography (CT) of the brain, between 1986 and 2000. All CT scans were examined for arachnoid cysts. Headache, dizziness, history of head trauma, dementia, depression, epilepsy, and hip fracture were assessed using data from clinical examinations, interviews and the Swedish hospital discharge register. Cognition was assessed using the Mini-Mental Status Examination, and depressive symptoms using the Montgomery–Åsberg Depression Rating Scale. Date of death was obtained from the National Swedish Death Registry. The prevalence of arachnoid cysts was 2.3 % (
n
= 29), with no significant difference between men and women. Probands with and without cysts had the same frequency of headache, dizziness, previous head trauma, cognitive impairment, and depressive symptoms. Furthermore, there were no differences regarding the prevalence of dementia, depression, epilepsy, or previous hip fracture. Arachnoid cysts were not associated with increased mortality. Arachnoid cysts are common incidental finding, with the same rate in men and women, and are probably asymptomatic. The lack of relation with symptoms like headache, dizziness and cognitive impairment suggest caution in ascribing symptoms to incidentally discovered arachnoid cysts and a restrictive attitude to treatment.
Background
The objective was to evaluate the cost-effectiveness of shunt surgery in patients with idiopathic normal pressure hydrocephalus (iNPH).
Methods
Health-related quality of life was evaluated ...before and 6 months after surgery using the EQ-5D-3 L (EuroQOL group five-dimensions health survey) in 30 patients (median age, 71 years; range, 65–89 years) diagnosed with iNPH. The costs associated with shunt surgery were assessed by a detailed survey with interviews and extraction of register data concerning the cost of hospital care, primary care, residential care, home-care service and informal care. The cost of untreated patients was derived from the cost of dementia disorders in Sweden in 2012, as reported by the National Board of Health and Welfare. The cost effectiveness analysis used a decision-analytic Markov model. We used a societal perspective and a lifelong time horizon to estimate costs and effects. One-way sensitivity analysis and probabilistic sensitivity analysis were carried out to test the robustness of the model.
Results
The shunt surgery model as the standard treatment in iNPH resulted in a gain of 2.2 life years and 1.7 quality-adjusted life years (QALY), along with an incremental cost per patient of €7,500/QALY. The sensitivity analysis showed that the results were not sensitive to changes in uncertain parameters or assumptions.
Conclusions
Shunt surgery in iNPH, an underdiagnosed condition severely impairing elderly patients, is not only an effective medical treatment, it is also cost-effective, adding 2.2 additional life years and 1.7 QALYs at a low cost, a remarkable gain for an individual aged around 70 years.
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