Reappraisal of the intracranial pressure and cerebrospinal fluid dynamics in patients with the so-called “Normal pressure hydrocephalus” syndrome

Summary Fifty-four shunt-responsive patients were selected from a prospective protocol directed to study patients with suspected normal pressure hydrocephalus (NPH). Patients with gait disturbances, dementia, non-responsive L-Dopa Parkinsonism, urinary or faecal incontinence and an Evans ratio greater or equal to 0.30 on the CT scan were included in the study.As a part of their work-up all patients underwent intracranial pressure monitoring and hydrodynamic studies using Marmarou's bolus test. According to mean intracranial pressure (ICP) and the percentage of high amplitude B-waves, patients were subdivided in the following categories: 1) Active hydrocephalus (mean ICP above 15 mmHg), which is in fact no tone normal pressure hydrocephalus; 2) Compensated unstable hydrocephalus, when mean ICP was below 15 mmHg and B-waves were present in more than 25% of the total recording time and 3) Compensated stable hydrocephalus when ICP was lower or equal to 15 mmHg and beta waves were present in less than 25% of the total recording time.The majority of the patients in this study (70%) presented continuous high or intermittently raised ICP (active or unstable compensated hydrocephalus group). Mean resistance to outflow of CSF (Rout) was 38.8 mm Hg/ml/min in active hydrocephalus and 23.5 mm Hg/ml/min in the compensated group (Students t-test, p < 0.05). Higher resistance to outflow was found in patients with obliterated cortical sulci and obliterated Sylvian cisterns in the CT scan.No statistically significant correlation was found when plotting the percentage of beta waves against pressure volume index (PVI), compliance or Rout. An exponential correlation was found when plotting beta waves against the sum of conductance to outflow and compliance calculated by PVI method (r=0.79).Patients with the so-called normal pressure hydrocephalus syndrome have different ICP and CSF dynamic profiles. Additional studies taking into consideration these differences are necessary before defining the sensitivity, specificity and predictive value of ICP monitoring and CSF studies in selecting appropriate candidates for shunting.     

Normal pressure hydrocephalus. Influences on cerebral hemodynamic and cerebrospinal fluid pressure--chemical autoregulation

Blood flow in the cerebral gray matter was measured in normal pressure hydrocephalus and Alzheimer disease by 133Xe inhalation. Flow values in the frontal and temporal gray matter increased after lowering cerebrospinal fluid (CSF) pressure by lumbar puncture in normal pressure hydrocephalus (p less than 0.05) and also after shunting. One case with cerebral complications did not improve clinically. In Alzheimer disease the reverse (decreases in flow in the gray matter) occurred after removal of CSF. Normal pressure hydrocephalus was associated with impaired cerebral vasomotor responsiveness during 100% oxygen and 5% carbon dioxide inhalation. This complication was restored toward normal after CSF removal and/or shunting. Cerebral blood flow measurements appear to be useful for confirming the diagnosis of normal pressure hydrocephalus and predicting the clinical benefit from shunting.     

Idiopathic normal pressure hydrocephalus: Analysis of factors related to cerebrospinal fluid dynamics determining functional prognosis

Summary This investigation has been undertaken to analyze the findings with both the cerebrospinal fluid (CSF) pressure (Pcsf) and CSF pulse pressure (PP) in order to predict the outcome of patients with the syndrome of idiopathic normal pressure hydrocephalus (NPH). Accordingly, a prospective clinical study was planned in which two groups of patients with NPH, having analogous prevalence of several matched clinical and radiological parameters, were separated on the basis of their positive or negative response to shunting. Both the resting Pcsf and CSF PP profiles were compared in these two groups, and between them and normal controls. CSF PP amplitude and CSF PP latency correlated directly in conditions associated with either normal or high compliance (controls and patients with Alzheimer-like disorders), whereas this correlation was inverse in states of low compliance (NPH). On the other hand, shunt-responders showed a resting Pcsf significantly higher than both non-responders and controls.The following conclusions were obtained: 1) CSF PP is a high-amplitude and relative low-latency wave in NPH when compared with controls; 2) CSF PP amplitude and latency correlate directly in normal subjects and in those with primary cerebral atrophy; 3) a non-reversible stage of NPH could be conceived in contradistinction to the reversible one, in both of which an inverse correlation between the amplitude and the latency takes place, the main difference between them being the resting Pcsf, which is significantly lower in the former than in the latter, depending on the degree of atrophic changes developed.     

Link between vasogenic waves of intracranial pressure and cerebrospinal fluid outflow resistance in normal pressure hydrocephalus

Recent studies on normal pressure hydrocephalus (NPH) have pointed to a possible link between the disturbance in CSF circulation and cerebrovascular factors. We investigated the quantitative relationship between the resistance to CSF outflow (Rcsf) and vasogenic waves of ICP in patients with normal pressure hydrocephalus. Forty-five patients with NPH were investigated by an infusion study. The magnitudes of vasogenic ICP components: pulse, respiratory and slow vasogenic waves were assessed, and compared with Rcsf. Both baseline respiratory and slow waves of ICP were positively correlated with Rcsf. The respiratory wave at baseline was a single independent predictor of Rcsf (r = 0.66, p < 0.0002). All vasogenic components increased significantly during the infusion test. The magnitude of the increase was positively correlated with Rcsf. The vasogenic ICP waves, notably the respiratory wave of ICP, correlate with the resistance to CSF outflow.     

Treatment of normal pressure hydrocephalus with low versus medium pressure cerebrospinal fluid shunts

In a retrospective study, 39 patients received a low pressure (20 to 50 mm H2O) shunt and 33 received a medium pressure (55 to 85 mm H2O) shunt for the treatment of normal pressure hydrocephalus (NPH). Pre- and postoperative computed tomographic scans were obtained in 32 patients, permitting us to determine the influence of shunt pressure on ventricular size. A reduction in 3rd ventricle width was found to correlate with clinical improvement and was observed more frequently after the placement of a low pressure shunt than after the placement of a medium pressure shunt. When results were evaluated in patients who did not have advanced NPH or develop postoperative complications, gait was markedly improved in 60% of those receiving a low pressure shunt as opposed to 23% of those receiving a medium pressure shunt (P less than 0.05).     

Lumbar cerebrospinal fluid pressure waves versus intracranial pressure waves in idiopathic normal pressure hydrocephalus

The aim of this study was to explore how the lumbar cerebrospinal fluid pressure (CSFP) waves recorded during lumbar infusion compared with the intracranial pressure (ICP) waves recorded, either during lumbar infusion or during long-term, overnight monitoring. For this purpose, we assessed 27 simultaneous lumbar CSFP/ICP recordings made during lumbar infusion and 27 long-term, overnight ICP recordings in 27 consecutive idiopathic normal pressure hydrocephalus (iNPH) patients. Pressure waves during lumbar infusion were explored by computing pulse pressure amplitude and mean single wave pressure of every corresponding CSFP/ICP wave pair; among our 27 lumbar CSFP/ICP recordings a total of 35,532 CSFP/ICP wave pairs were available for analysis. We as well computed mean values of pulse pressure amplitude (i.e. mean CSFP wave amplitude or mean ICP wave amplitude) and mean values of mean single wave pressure (i.e. mean CSFP or mean ICP) during consecutive 6-s time windows, as well as average values for the individual recordings. During lumbar infusion, the cerebrospinal fluid pulse pressure amplitudes were about 2 mmHg smaller than the corresponding intracranial pulse pressure amplitudes. The mean CSFP wave amplitudes recorded during lumbar infusion correlated significantly with the mean ICP wave amplitudes recorded either during lumbar infusion or during long-term, overnight ICP monitoring. In 21 of 27 lumbar infusion tests (78%), the presence of elevated lumbar mean CSFP waves was related to presence of elevated mean ICP wave amplitudes during long-term, overnight ICP monitoring. Hence, the lumbar cerebrospinal fluid pulse pressure amplitudes recorded during lumbar infusion could be used to predict the intracranial pulse pressure amplitudes recorded during long-term, overnight ICP monitoring.     

Normal pressure hydrocephalus: relationship among clinical picture, CT scan and intracranial pressure monitoring

Fifty-five patients suffering from normal pressure hydrocephalus were considered. All patients underwent chronic intracranial pressure (ICP) monitoring for at least 24 h. The decision to perform surgery was made on the basis of the ICP monitoring data only. A retrospective analysis on clinical pictures, CT findings and ICP monitoring data was carried out in the attempt to find more selective criteria, in order to submit patients to chronic ICP monitoring. Clinical findings showed controversial data, whereas the enlargement of the III ventricle showed a strict, but not absolute, correlation to pathological pressure profiles. The follow-up of non-shunted patients is briefly discussed.     

Intracranial cerebrospinal fluid distribution and its postoperative changes in normal pressure hydrocephalus

Summary  Background. This study was conducted to investigate the usefulness of intracranial cerebrospinal fluid (CSF) volume measurement using MR-based methods in the management of patients with normal pressure hydrocephalus (NPH).  Methods. The study group comprised 19 patients with NPH who showed a favorable outcome after ventricular shunting, 15 normal volunteers (NV), and 15 patients with cerebrovascular disease (CVD). A 3D-fast asymmetric spin echo MR imaging sequence and the region-growing method were used to extract the CSF space from MR images. Ventricular volume (VV) and intracranial CSF volume (ICV) were measured and the VV/ICV ratio was calculated in each case. In NPH patients, the CSF volume was measured again after shunting.  Findings. The mean VV and VV/ICV ratio in the NPH group (91.1 mL and 45.2%, respectively) were significantly (p<0.01) higher than those in the NV group (26.5 mL and 13.7%) and in the CVD group (44.5 mL and 17.8%). On the other hand, mean ICV values were not significantly different among the three groups. The VV was markedly decreased postoperatively (mean −40.7%), whereas the ICV was unchanged, resulting in a marked reduction in the VV/ICV ratio (mean −39.3%).  Interpretation. These results suggest that patients with NPH have a unique intracranial CSF distribution, with an enlarged VV and a slightly increased ICV, resulting in a high VV/ICV ratio. Shunting led to dramatic improvement in our patients. It is likely that CSF measurement can provide valuable information in the management of patients with NPH.     

Intracranial pressure and conductance to outflow of cerebrospinal fluid in normal-pressure hydrocephalus.

Forty patients with clinical evidence of normal-pressure hydrocephalus were studied by monitoring intraventricular pressure during a 24-hour period, and by a lumboventricular perfusion test for measurement of the conductance to outflow of cerebrospinal fluid (CSF). The purpose of the study was to investigate whether there is a relationship between intraventricular pressure and conductance to outflow of CSF, and whether it is possible to use the results from pressure monitoring in the selection of patients who may be expected to benefit from shunting therapy. The conductance to outflow was used as an evaluation factor in the selection of patients to be treated by a shunt. The conductance to CSF outflow differed by twelvefold between the lowest and highest values. The level of resting intraventricular pressure was within normal limits in all patients. Accordingly, there was no evidence of a relationship between conductance to outflow and intraventricular pressure. So-called B-waves were seen more frequently in patients with decreased conductance to outflow, but were also present in patients with high conductance to outflow. Therefore, the presence of B-waves does not imply a low conductance to outflow of CSF.     

Relationship between shunt-dependent hydrocephalus after subarachnoid haemorrhage and duration of cerebrospinal fluid drainage

Subarachnoid haemorrhage (SAH) patients in Fisher group 3 have a high risk of vasospasm and chronic hydrocephalus. We have provided cisternal irrigation combined with a head-shaking method for preventing vasospasm in SAH patients. We investigated 76 SAH patients in Fisher group 3 who received cisternal irrigation with head-shaking to evaluate the relationship between the occurrence of hydrocephalus and various clinical factors, including duration of cerebrospinal fluid (CSF) drainage. Chronic hydrocephalus occurred in 25 patients (33%). The occurrence of hydrocephalus was associated with longer duration of CSF drainage (median, 13 days versus 9 days). By logistic regression analysis using significant factors, including age, preoperative neurological grade and Glasgow Outcome Scale, only the duration of drainage was independently associated with the occurrence of hydrocephalus (Odds ratio = 1.18 per day; 95% confidence interval, 1.02- 1.36). These results indicate that long duration of CSF drainage for preventing vasospasm may increase the occurrence of hydrocephalus.     

Analysis of potential diagnostic biomarkers in cerebrospinal fluid of idiopathic normal pressure hydrocephalus by proteomics

Summary Background. The pathogenesis of idiopathic normal pressure hydrocephalus (INPH) is unknown, and the syndrome of INPH remains a diagnostic and therapeutic challenge. The present study investigated the disease-specific proteins that aid in the diagnosis and treatment of INPH and thus to study their role in the disease process. Methods. A comparative proteomic analysis was used for clinical screening of cerebrospinal fluid (CSF) proteins in 15 patients with INPH and compared with 12 normal subjects. Furthermore, enzyme linked immunosorbent assay (ELISA) was performed for comparison with CSF proteins between individual INPH patients and controls. Results. Seven proteins and their isoforms, including leucine-rich α-2-glycoprotein (LRG), α1-antichymotrypsin, apolipoprotein D, apolipoprotein J, haptoglobin α1, serum albumin, and α-1-microglobulin/bikunin precursor showed significant changes in CSF of INPH patients compared with controls by proteomic analysis. And significant higher CSF levels of LRG in INPH patients compared with controls were found by ELISA. Conclusions. These results indicate that there are significant differences in the expression of certain proteins in the CSF of patients with INPH and normal subjects. In particular, the CSF level assay of LRG suggests that LRG is a specific biomarker for INPH and has potential use in the diagnosis and indication for CSF shunting.