Background

Levels of the biomarkers amyloid-β 1–42 (Aβ42), tau and phosphorylated tau (p-tau) are decreased in the cerebrospinal fluid (CSF) of patients with idiopathic normal pressure hydrocephalus (iNPH). The mechanism behind this is unknown, but one potential explanation is dilution by excessive CSF volumes. The aim of this study was to investigate the presence of a dilution effect, by studying the relationship between ventricular volume (VV) and the levels of the CSF biomarkers.

Methods

In this cross-sectional observational study, preoperative magnetic resonance imaging (MRI) and lumbar CSF was acquired from 136 patients with a median age of 76 years, 89 men and 47 females, selected for surgical treatment for iNPH. The CSF volume of the lateral and third ventricles was segmented on MRI and related to preoperative concentrations of Aβ42, tau and p-tau.

Results

In the total sample VV (Median 140.7 mL) correlated weakly (r_s = − 0.17) with Aβ42 (Median 534 pg/mL), but not with tau (Median 216 pg/mL) nor p-tau (Median 31 pg/mL). In a subgroup analysis, the correlation between VV and Aβ42 was only present in the male group (r_s = − 0.22, p = 0.038). Further, Aβ42 correlated positively with tau (r_s = 0.30, p = 0.004) and p-tau (r_s = 0.26, p = 0.012) in males but not in females.

Conclusions

The findings did not support a major dilution effect in iNPH, at least not in females. The only result in favor for dilution was a weak negative correlation between VV and Aβ42 but not with the other lumbar CSF biomarkers. The different results between males and females suggest that future investigations of the CSF pattern in iNPH would gain from sex-based subgroup analysis.

OBJECTIVE MRI volumetry could be used as an alternative to invasive tests of shunt function. In this study, the authors aimed to assess the difference in ventricular volume (VV) before and after surgery and at different performance levels (PLs) of the shunt. METHODS This study was a randomized, double-blind trial with a crossover design. The study sample consisted of 36 patients (25 men, 11 women) with a median age of 76 years. All patients had idiopathic normal pressure hydrocephalus (iNPH) and received a Strata shunt at the regional hospital in & Ouml;stersund, Sweden, with an initial PL of 1.5. Participants underwent MRI with volumetric sequences before surgery and four times postoperatively: at 1 month before randomization to either PL 1.0 (n = 15) or 2.5 (n = 17); at 2 months before crossover to PL 2.5 or 1.0; at 3 months before lowering the PL to 0.5; and finally, at 3 months and 1 day after surgery before resetting the PL to 1.5. VV was measured semiautomatically using quantitative MRI. Both the patient and the examiner of clinical tests and volumetry were blinded to the PL. RESULTS VV changed significantly between the presurgical level (median 129 ml) and the different shunt settings, i.e., PL 1.0 (median 115 ml), 1.5 (median 120 ml), and 2.5 (median 128 ml; p < 0.001). A unidirectional change in VV was observed for all participants between PL 1.0 and PL 2.5 (median 12 ml, range 2.1-40.7 ml, p < 0.001). No significant change was noted in VV after 24 hours at PL 0.5. Eight participants had asymptomatic subdural effusions at PL 1.0. CONCLUSIONS The consistent decrease in VV after shunt surgery and between PL 2.5 and 1.0 supports the idea that MRI volumetry could be a noninvasive method for evaluating shunt function in iNPH, preventing unnecessary shunt revisions. However, further studies on retest variability of VV as well as verification against advanced testing of shunt function are needed before a clinical implementation of this method can be performed.

Sleepiness and apathy are often reported in patients with normal pressure hydrocephalus. However, research on outcomes after shunt surgery has mainly focused on the classical triad symptoms, that is, gait, cognition, and bladder dysfunction. This study aimed to describe the effects of shunt treatment on excessive daytime sleepiness and whether there was a relation to changes in ventricular volume. Pre- and postsurgical excessive daytime sleepiness was investigated using the Epworth sleepiness scale in a sample of 32 patients with normal pressure hydrocephalus who underwent shunt surgery. Data were gathered before surgery and at 1, 2, and 3 months after surgery and with different settings of the shunt. In the total sample, the Epworth sleepiness scale improved by a median of 1.5 points at 1 month after surgery, p = 0.026. The improvement was predominately found in the group (n = 6) with high presurgical daytime sleepiness (Epworth sleepiness scale >12) (median = 12 points, p = 0.035) compared with a median change of 0 points (p = 0.47) in the group with Epworth sleepiness scale <= 12 (n = 26). Between the postsurgical follow-ups, no further change in the Epworth sleepiness scale score was observed. The Epworth sleepiness scale score did not correlate with clinical tests nor with ventricular volume. Daytime sleepiness seems to be another domain of normal pressure hydrocephalus symptomatology in addition to the classical triad that is responsive to treatment, at least when pronounced. The Epworth sleepiness scale is a quick test to administer and could be a valuable addition to pre-surgical screening for treatable symptoms.