Global Cerebral Autoregulation, Resistance to Cerebrospinal Fluid Outflow and Cerebrovascular Burden in Normal Pressure Hydrocephalus.

INTRODUCTION: We previously examined the relationship between global autoregulation pressure reactivity index (PRx), mean arterial blood pressure (ABP), Resistance to cerebral spinal fluid (CSF) outflow (Rout) and their possible effects on outcome after surgery on 83 shunted patients. In this study, we aimed to quantify the relationship between all parameters that influence Rout, their interaction with the cerebral vasculature, and their role in shunt prognostication. METHODS: From 423 patients having undergone infusion tests for possible NPH, we selected those with monitored ABP and calculated its mean and PRx. After shunting, 6 months patients' outcome was marked using a simple scale (improvement, temporary improvement, and no improvement). We explored the relationship between age, different CSF dynamics variables, and vascular parameters using multivariable models. RESULTS: Rout had a weaker predictive value than ABP (Fisher Discrimination Ratio of 0.02 versus 0.42). ABP > 98 was an independent predictor of shunt outcome with odd ratio 6.4, 95% CI: 1.8-23.4 and p-value = 0.004. There was a strong and significant relationship between the interaction of age, PRx, ABP, and Rout (R = 0.53 with p = 7.28 × 10-0.5). Using our linear model, we achieved an AUC 86.4% (95% CI: 80.5-92.3%) in detecting shunt respondents. The overall sensitivity was 94%, specificity 75%, positive predictive value (PPV) of 54%, and negative predictive value of 97%. CONCLUSION: In patients with low Rout and high cerebrovascular burden, as described by high ABP and disturbed global autoregulation, response to shunting is less likely. The low PPV of high resistance, preserved autoregulation and absence of hypertension could merit further exploration.

Comparison of Assessment for Shunting with Infusion Studies Versus Extended Lumbar Drainage in Suspected Normal Pressure Hydrocephalus.

INTRODUCTION: Tools available for diagnosis of normal pressure hydrocephalus (NPH) and prediction of shunt-response are overnight ICP monitoring, infusion studies, and extended lumbar drainage (ELD). We investigated the shunt-response predictive value by infusion tests versus ELD. MATERIAL AND METHODS: We retrospectively recruited 83 patients who had undergone both infusion study and ELD assessments and compared infusion study hydrodynamics with improvement at clinic follow-up after ELD and after shunting. RESULTS: 62 patients had Rout >11 mmHg/mL/min. 28 Showed physiotherapy-documented improvement following ELD, and were selected for shunting, of which 21 were shunted. Of these, 19 showed improvement. Eight patients with Rout >20 mmHg/mL/min showed no response to ELD and were not shunted.There were 21 patients with Rout <11 mmHg/mL/min: five were shunted, showed improvement at follow-up, and had Rout >6 mmHg/mL/min. ICP amplitude did not differ at baseline or plateau between responders and non-responders. CONCLUSIONS: ELD response and CSF dynamics differed remarkably. All patients with Rout <6 mmHg/mL/min showed no improvement with ELD, indicating that ELD and shunting might be contraindicated in these subjects. High Rout patients with no response to ELD could merit further consideration.

The Role of Cerebrospinal Fluid Dynamics in Normal Pressure Hydrocephalus Diagnosis and Shunt Prognostication.

BACKGROUND: Over the years, there have been several reports and trials of the resistance to cerebrospinal fluid (CSF) outflow (Rout) in normal pressure hydrocephalus (NPH). This work aimed to revisit the utility of testing CSF circulation in a large population of patients clinically presenting with NPH. MATERIALS AND METHODS: We retrospectively analyzed the data of 369 NPH patients-either shunted or with endoscopic third ventriculostomy (ETV)-in Cambridge between 1992 and 2018. We determined the patients' outcomes (improvement versus no improvement at 6 months) by applying a threshold on R out values and compared our results with those of existing literature. We also conducted a correlation analysis between all variables and calculated Chi-Statistics (as a measure of separability between improvement and no improvement outcomes) to determine a subset of variables which achieved the highest accuracy in prediction of outcome. RESULTS: In our dataset, R out of 18 mmHg*min/mL achieved the highest Chi-statistics of 9.7 with p-value <0.01 when adjusted for age. In addition to R out, intracranial pressure (ICP) values at the baseline and plateau, CSF production rate and ICP amplitude to slope ratio showed significant Chi-Statistics values (more than 5). Using these variables, an overall accuracy of 0.70 ± 0.09 was achieved for prediction of the shunt outcome. CONCLUSION: Rout can be used for selecting patients for shunt surgery but not for excluding patients from treatment. Critical, multivariable approaches are required to comprehend CSF dynamics and pressure-volume compensation in NPH. Outcome definition and assessment could also be brought to question.

Errors and Consequences of Inaccurate Estimation of Mean Blood Flow Velocity in Cerebral Arteries.

Many transcranial Doppler ultrasonography devices estimate the mean flow velocity (FVm) by using the traditional formula (FVsystolic + 2 × FVdiastolic)/3 instead of a more accurate formula calculating it as the time integral of the current flow velocities divided by the integration period. We retrospectively analyzed flow velocity and intracranial pressure signals containing plateau waves (transient intracranial hypertension), which were collected from 14 patients with a traumatic brain injury. The differences in FVm and its derivative pulsatility index (PI) calculated with the two different methods were determined. We found that during plateau waves, when the intracranial pressure (ICP) rose, the error in FVm and PI increased significantly from the baseline to the plateau (from 4.6 ± 2.4 to 9.8 ± 4.9 cm/s, P < 0.05). Similarly, the error in PI also increased during plateau waves (from 0.11 ± 0.07 to 0.44 ± 0.24, P < 0.005). These effects were most likely due to changes in the pulse waveform during increased ICP, which alter the relationship between systolic, diastolic, and mean flow velocities. If a change in the mean ICP is expected, then calculation of FVm with the traditional formula is not recommended.

Lower Breakpoint of Intracranial Amplitude-Pressure Relationship in Normal Pressure Hydrocephalus.

The relationship between intracranial pulse amplitude (AMP) and mean intracranial pressure (ICP) has been previously described. Generally, AMP increases proportionally to rises in ICP. However, at low ICP a lower breakpoint (LB) of amplitude-pressure relationship can be observed, below which pulse amplitude stays constant when ICP varies. Theoretically, below this breakpoint, the pressure-volume relationship is linear (good compensatory reserve, brain compliance stays constant); above the breakpoint, it is exponential (brain compliance decreases with rising ICP).Infusion tests performed in 169 patients diagnosed for idiopathic normal pressure hydrocephalus (iNPH) during the period 2004-2013 were available for analysis. A lower breakpoint was observed in 62 patients diagnosed for iNPH. Improvement after shunt surgery in patients in whom LB was recorded was 77% versus 90% in patients where LB was absent (p < 0.02). There was no correlation between improvement and slope of amplitude-pressure line above LB.The detection of a lower breakpoint is associated with less frequent improvement after shunting in NPH. It may be interpreted that cerebrospinal fluid dynamics of patients working on the flat part of the pressure-volume curve and having a 'luxurious' compensatory reserve, are more frequently caused by brain atrophy, which is obviously not responding to shunting.

Differences in Cerebrospinal Fluid Dynamics in Posttraumatic Hydrocephalus Versus Atrophy, Including Effect of Decompression and Cranioplasty.

INTRODUCTION: Challenges in diagnosing post-traumatic hydrocephalus (PTH) have created a need for an accurate diagnostic tool. We aim to report CSF dynamics in PTH and atrophy, along with differences before and after cranioplasty. METHODS: We retrospectively analyzed traumatic brain injury patients with ventriculomegaly who had infusion studies. We divided patients depending on CSF dynamics into two groups: 'likely PTH' (A) and 'likely atrophy' (B). A group of idiopathic normal pressure hydrocephalus shunt-responsive patients was used for comparison (C). RESULTS: Group A consisted of 36 patients who were non-decompressed or had a cranioplasty in situ for over 1 month. Group B included 16 patients with low Rout, AMP, and dAMP, 9 of whom were decompressed. Rout and dAMP were significantly higher in Group A than B, but significantly lower than Group C (45 iNPH patients). RAP change during infusion in group A indicated depleted compensatory reserve compared to ample reserve in group B. Repeat studies in five decompressed patients post-cranioplasty showed all parameters increased. CONCLUSIONS: Infusion tests are not useful in decompressed patients, whilst cranioplasty allowed differentiation between possible PTH and atrophy. Rout and AMP were significantly lower in PTH compared to iNPH and did not always reflect the degree of hydrocephalus reported on imaging.

Single Center Experience in Cerebrospinal Fluid Dynamics Testing.

Normal pressure hydrocephalus is more complex than a simple disturbance of the cerebrospinal fluid (CSF) circulation. Nevertheless, an assessment of CSF dynamics is key to making decisions about shunt insertion, shunt malfunction, and for further management if a patient fails to improve. We summarize our 25 years of single center experience in CSF dynamics assessment using pressure measurement and analysis. 4473 computerized infusion tests have been performed. We have shown that CSF infusion studies are safe, with incidence of infection at less than 1%. Raised resistance to CSF outflow positively correlates (p < 0.014) with improvement after shunting and is associated with disturbance of cerebral blood flow and its autoregulation (p < 0.02). CSF infusion studies are valuable in assessing possible shunt malfunction in vivo and for avoiding unnecessary revisions. Infusion tests are safe and provide useful information for clinical decision-making for the management of patients suffering from hydrocephalus.

Influence of mild-moderate hypocapnia on intracranial pressure slow waves activity in TBI.

BACKGROUND: In traumatic brain injury (TBI) the patterns of intracranial pressure (ICP) waveforms may reflect pathological processes that ultimately lead to unfavorable outcome. In particular, ICP slow waves (sw) (0.005-0.05 Hz) magnitude and complexity have been shown to have positive association with favorable outcome. Mild-moderate hypocapnia is currently used for short periods to treat critical elevations in ICP. Our goals were to assess changes in the ICP sw activity occurring following sudden onset of mild-moderate hypocapnia and to examine the relationship between changes in ICP sw activity and other physiological variables during the hypocapnic challenge. METHODS: ICP, arterial blood pressure (ABP), and bilateral middle cerebral artery blood flow velocity (FV), were prospectively collected in 29 adult severe TBI patients requiring ICP monitoring and mechanical ventilation in whom a minute volume ventilation increase (15-20% increase in respiratory minute volume) was performed as part of a clinical CO2-reactivity test. The time series were first treated using FFT filter (pass-band set to 0.005-0.05 Hz). Power spectral density analysis was performed. We calculated the following: mean value, standard deviation, variance and coefficient of variation in the time domain; total power and frequency centroid in the frequency domain; cerebrospinal compliance (Ci) and compensatory reserve index (RAP). RESULTS: Hypocapnia led to a decrease in power and increase in frequency centroid and entropy of slow waves in ICP and FV (not ABP). In a multiple linear regression model, RAP at the baseline was the strongest predictor for the decrease in the power of ICP slow waves (p < 0.001). CONCLUSION: In severe TBI patients, a sudden mild-moderate hypocapnia induces a decrease in mean ICP and FV, but also in slow waves power of both signals. At the same time, it increases their higher frequency content and their morphological complexity. The difference in power of the ICP slow waves between the baseline and the hypocapnia period depends on the baseline cerebrospinal compensatory reserve as measured by RAP.

Observational study of intracranial pressure instability in patients with pseudotumour cerebri syndrome.

Introduction: A fixed CSF pressure (CSFp) of 25 cmH2O (18 mmHg) has been utilised to date to define and classify pseudotumour cerebri syndrome (PTCS). Furthermore, ICP monitoring, and CSF infusion tests have not been frequently performed in this group of patients. Research question: We aimed to report typical, unusual and unstable patterns of ICP in patients with PTCS. Material and methods: We reviewed the recordings of CSF infusion tests and overnight ICP monitoring of patients with suspected or confirmed IIH between January 2003-December 2020.We excluded all patients with a shunt in situ and selected recordings that represented unstable patterns of ICP changes in PTCS. Results: 463 CSF infusion tests and 26 ICP monitorings of PTCS patients had been performed in this timeframe. We divided results of observed pattern into two group: those with known venous sinus measurements (Group A) and those without (Group B). Observed recordings formed a total of 5 and 4 different patterns respectively, based on the behaviour of ICP and slow waves at rest, overnight, and during infusion as well as in relationship to the clinical presentation of each patient. Discussion and conclusion: Accurate monitoring of ICP in PTCS is quintessential. Full understanding of each element of its pathophysiology and their interaction would be essential and include quantification of the CSF pressure not only as a number, but also with consideration of its dynamic contents. Cerebral venous pressure measurements and/or monitoring may be useful. Consideration of the presence or absence of papilloedema in the context of disturbed CSF dynamics could reveal further diagnostic and therapeutic insights.

Cerebrospinal fluid dynamics in non-acute post-traumatic ventriculomegaly.

BACKGROUND: Post-traumatic hydrocephalus (PTH) is potentially under-diagnosed and under-treated, generating the need for a more efficient diagnostic tool. We aim to report CSF dynamics of patients with post-traumatic ventriculomegaly. MATERIALS AND METHODS: We retrospectively analysed post-traumatic brain injury (TBI) patients with ventriculomegaly who had undergone a CSF infusion test. We calculated the resistance to CSF outflow (Rout), AMP (pulse amplitude of intracranial pressure, ICP), dAMP (AMPplateau-AMPbaseline) and compensatory reserve index correlation coefficient between ICP and AMP (RAP). To avoid confounding factors, included patients had to be non-decompressed or with cranioplasty > 1 month previously and Rout > 6 mmHg/min/ml. Compliance was assessed using the elasticity coefficient. We also compared infusion-tested TBI patients selected for shunting versus those not selected for shunting (consultant decision based on clinical and radiological assessment and the infusion results). Finally, we used data from a group of shunted idiopathic Normal Pressure Hydrocephalus (iNPH) patients for comparison. RESULTS: Group A consisted of 36 patients with post-traumatic ventriculomegaly and Group B of 45 iNPH shunt responders. AMP and dAMP were significantly lower in Group A than B (0.55 ± 0.39 vs 1.02 ± 0.72; p < 0.01 and 1.58 ± 1.21 vs 2.76 ± 1.5; p < 0.01. RAP baseline was not significantly different between the two. Elasticity was higher than the normal limit in all groups (average 0.18 1/ml). Significantly higher Rout was present in those with probable PTH selected for shunting compared with unshunted. Mild/moderate hydrocephalus, ex-vacuo ventriculomegaly/encephalomalacia were inconsistently reported in PTH patients. CONCLUSIONS: Rout and AMP were significantly lower in PTH compared to iNPH and did not always reflect the degree of hydrocephalus or atrophy reported on CT/MRI. Compliance appears reduced in PTH.