Congenital hydrocephalus: a review of recent advances in genetic etiology and molecular mechanisms.

The global prevalence rate for congenital hydrocephalus (CH) is approximately one out of every five hundred births with multifaceted predisposing factors at play. Genetic influences stand as a major contributor to CH pathogenesis, and epidemiological evidence suggests their involvement in up to 40% of all cases observed globally. Knowledge about an individual's genetic susceptibility can significantly improve prognostic precision while aiding clinical decision-making processes. However, the precise genetic etiology has only been pinpointed in fewer than 5% of human instances. More occurrences of CH cases are required for comprehensive gene sequencing aimed at uncovering additional potential genetic loci. A deeper comprehension of its underlying genetics may offer invaluable insights into the molecular and cellular basis of this brain disorder. This review provides a summary of pertinent genes identified through gene sequencing technologies in humans, in addition to the 4 genes currently associated with CH (two X-linked genes L1CAM and AP1S2, two autosomal recessive MPDZ and CCDC88C). Others predominantly participate in aqueduct abnormalities, ciliary movement, and nervous system development. The prospective CH-related genes revealed through animal model gene-editing techniques are further outlined, focusing mainly on 4 pathways, namely cilia synthesis and movement, ion channels and transportation, Reissner's fiber (RF) synthesis, cell apoptosis, and neurogenesis. Notably, the proper functioning of motile cilia provides significant impulsion for cerebrospinal fluid (CSF) circulation within the brain ventricles while mutations in cilia-related genes constitute a primary cause underlying this condition. So far, only a limited number of CH-associated genes have been identified in humans. The integration of genotype and phenotype for disease diagnosis represents a new trend in the medical field. Animal models provide insights into the pathogenesis of CH and contribute to our understanding of its association with related complications, such as renal cysts, scoliosis, and cardiomyopathy, as these genes may also play a role in the development of these diseases. Genes discovered in animals present potential targets for new treatments but require further validation through future human studies.

Embracing uncertainty in cerebrospinal fluid dynamics: A Bayesian approach to analysing infusion studies.

Introduction: Cerebrospinal fluid (CSF) infusion test analysis allows recognizing and appropriately evaluating CSF dynamics in the context of normal pressure hydrocephalus (NPH), which is crucial for effective diagnosis and treatment. However, existing methodology possesses drawbacks that may compromise the precision and interpretation of CSF dynamics parameters. Research question: This study aims to circumvent these constraints by introducing an innovative analysis method grounded in Bayesian inference. Material and methods: A single-centre retrospective cohort study was conducted on 858 patients who underwent a computerized CSF infusion test between 2004 and 2020. We developed a Bayesian framework-based method for parameter estimation and compared the results to the current, gradient descent-based approach. We evaluated the accuracy and reliability of both methods by analysing erroneous prediction rates and curve fitting errors. Results: The Bayesian method surpasses the gradient descent approach, reflected in reduced inaccurate prediction rates and an improved goodness of model fit. On whole cohort level both techniques produced comparable results. However, the Bayesian method holds an added advantage by providing uncertainty intervals for each parameter. Sensitivity analysis revealed significance of the CSF production rate parameter and its interplay with other variables. The resistance to CSF outflow demonstrated excellent robustness. Discussion and conclusion: The proposed Bayesian approach offers a promising solution for improving robustness of CSF dynamics assessment in NPH, based on CSF infusion tests. Additional provision of the uncertainty measure for each diagnostic metric may perhaps help to explain occasional poor diagnostic performance of the test, offering a robust framework for improved understanding and management of NPH.

Assessment of CSF Dynamics Using Infusion Study: Tips and Tricks.

Idiopathic normal pressure hydrocephalus, secondary chronic hydrocephalus, and other cerebrospinal fluid (CSF) disorders are often challenging to diagnose. Since shunt surgery is usually the only therapeutic option and carries significant morbidity, optimal patient selection is crucial. The tap test is the most commonly used prognostic test to confirm the diagnosis but lacks sensitivity. The lumbar infusion study (LIS) appears to be a better option, offering additional information on brain dynamics without increasing morbidity. However, this technique remains underused. In this narrative review, supported by the extensive experience of several European expert centers, we detail the physiological basis, indications, and CSF dynamics parameters that can be measured. We also discuss technical modalities and variations, including one versus 2 needles, patient positioning, and the site of CSF measurement, as well as in vivo shunt testing. Finally, we discuss the limitations and morbidity associated with the LIS. This review aims to assist teams wishing to incorporate LIS into their screening tools for chronic hydrocephalus and other CSF disorders.

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.

Cerebral hemodynamic monitoring combined with infusion test in hydrocephalus.

Introduction: Disturbance in cerebrospinal fluid (CSF) circulation may overlap with abnormality of cerebral blood flow (CBF) in hydrocephalus. Transcranial Doppler (TCD) ultrasonography is a non-invasive technique able to assess CBF velocity (CBFv) dynamics in response to a controlled rise in ICP during CSF infusion tests. Research question: Which TCD-derived cerebral hemodynamic parameters change during controlled rise of ICP, and in which direction? Material and methods: Infusion tests combined with TCD monitoring and non-invasive monitoring of arterial blood pressure (ABP) were conducted in 65 hydrocephalic patients. TCD-based hemodynamic variables: spectral pulsatility index (sPI), compliance of CSF space (Ci), cerebral autoregulation index (Mx), critical closing pressure (CrCP), cerebrovascular wall tension (WT) and diastolic closing margin (DCM-distance between diastolic ABP and CrCP) were calculated retrospectively. Results: During the test ICP increased on average to 25 mm Hg (p < 0.0001), with a parallel decrease in cerebral perfusion pressure (CPP, p < 0.0003). The CBFv waveform changed, showing a rise in sPI (p < 0.0001). Ci decreased inversely proportional to a rise in ICP, and correlated well with changes of compliance calculated from the Marmarou model. CrCP increased in response to rising ICP (p < 0.001) while WT decreased (p < 0.002). DCM correlated with cerebrospinal elasticity (R = -0.31; p < 0.04). Cerebral autoregulation was worse in patients with normal CSF circulation, measured as resistance to CSF outflow (Rout): Pearson correlation between Mx and Rout was R = -0.41; p < 0.02. Conclusion: A controlled rise in ICP affects cerebral hemodynamics in a moderate manner. Parameters like cerebral autoregulation index or DCM correlate with CSF dynamics and may be considered as supplementary variables for the diagnosis of hydrocephalus.

Brain blood flow pulse analysis may help to recognize individuals who suffer from hydrocephalus.

BACKGROUND: Normal pressure hydrocephalus (NPH) is often associated with altered cerebral blood flow. Recent research with the use of the ultrasonic method suggests specific changes in the shape of cardiac-related cerebral arterial blood volume (CaBV) pulses in NPH patients. Our study aims to provide a quantitative analysis of the shape of CaBV pulses, estimated based on transcranial Doppler ultrasonography (TCD) in NPH patients and healthy individuals. METHODS: The CaBV pulses were estimated using TCD cerebral blood flow velocity signals recorded from probable NPH adults and age-matched healthy individuals at rest. The shape of the CaBV pulses was compared to a triangular shape with 27 similarity parameters calculated for every reliable CaBV pulse and compared between patients and volunteers. The diagnostic accuracy of the most prominent parameter for NPH classification was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: The similarity parameters were calculated for 31 probable NPH patients (age: 59 years (IQR: 47, 67 years), 14 females) and 23 healthy volunteers (age: 54 years (IQR: 43, 61 years), 18 females). Eighteen of 27 parameters were different between healthy individuals and NPH patients (p < 0.05). The most prominent differences were found for the ascending slope of the CaBV pulse with the AUC equal to 0.87 (95% confidence interval: 0.77, 0.97, p < 0.001). CONCLUSIONS: The findings suggest that in NPH, the ascending slope of the CaBV pulse had a slower rise, was more like a straight line, and generally was less convex than in volunteers. Prospective research is required to verify the clinical utility of these findings.

Analysis of intracranial pressure pulse waveform in studies on cerebrospinal compliance: a narrative review.

Continuous monitoring of mean intracranial pressure (ICP) has been an essential part of neurocritical care for more than half a century. Cerebrospinal pressure-volume compensation, i.e. the ability of the cerebrospinal system to buffer changes in volume without substantial increases in ICP, is considered an important factor in preventing adverse effects on the patient's condition that are associated with ICP elevation. However, existing assessment methods are poorly suited to the management of brain injured patients as they require external manipulation of intracranial volume. In the 1980s, studies suggested that spontaneous short-term variations in the ICP signal over a single cardiac cycle, called the ICP pulse waveform, may provide information on cerebrospinal compensatory reserve. In this review we discuss the approaches that have been proposed so far to derive this information, from pulse amplitude estimation and spectral techniques to most recent advances in morphological analysis based on artificial intelligence solutions. Each method is presented with focus on its clinical significance and the potential for application in standard clinical practice. Finally, we highlight the missing links that need to be addressed in future studies in order for ICP pulse waveform analysis to achieve widespread use in the neurocritical care setting.

Managing Idiopathic Normal Pressure Hydrocephalus: Need for a Change of Mindset.

Idiopathic normal pressure hydrocephalus (iNPH) refers to a complex brain disorder characterized by ventricular enlargement and the classic Hakim's triad of gait and balance difficulties, urinary incontinence, and cognitive impairment. It predominantly affects older patients in the absence of an identified cause. As the elderly population continues to increase, iNPH becomes a growing concern in the complex spectrum of neuro-geriatric care, with significant socio-economic implications. However, unlike other well-structured management approaches for neurodegenerative disorders, the management of iNPH remains largely uncodified, leading to suboptimal care in many cases. In this article, we highlighted the challenges of current practice and identify key points for an optimal structuration of care for iNPH. Adopting a global approach to iNPH could facilitate a progressive shift in mindset, moving away from solely aiming to cure an isolated neurological disease with uncertain outcomes to providing comprehensive care that focuses on improving the daily life of frail patients with complex neurodegenerative burdens, using tailored goals.

Accuracy of Intracranial Pressure Monitoring-Single Centre Observational Study and Literature Review.

Intracranial hypertension and adequacy of brain blood flow are primary concerns following traumatic brain injury. Intracranial pressure (ICP) monitoring is a critical diagnostic tool in neurocritical care. However, all ICP sensors, irrespective of design, are subject to systematic and random measurement inaccuracies that can affect patient care if overlooked or disregarded. The wide choice of sensors available to surgeons raises questions about performance and suitability for treatment. This observational study offers a critical review of the clinical and experimental assessment of ICP sensor accuracy and comments on the relationship between actual clinical performance, bench testing, and manufacturer specifications. Critically, on this basis, the study offers guidelines for the selection of ICP monitoring technologies, an important clinical decision. To complement this, a literature review on important ICP monitoring considerations was included. This study utilises illustrative clinical and laboratory material from 1200 TBI patients (collected from 1992 to 2019) to present several important points regarding the accuracy of in vivo implementation of contemporary ICP transducers. In addition, a thorough literature search was performed, with sources dating from 1960 to 2021. Sources considered to be relevant matched the keywords: "intraparenchymal ICP sensors", "fiberoptic ICP sensors", "piezoelectric strain gauge sensors", "external ventricular drains", "CSF reference pressure", "ICP zero drift", and "ICP measurement accuracy". Based on single centre observations and the 76 sources reviewed in this paper, this material reports an overall anticipated measurement accuracy for intraparenchymal transducers of around ± 6.0 mm Hg with an average zero drift of <2.0 mm Hg. Precise ICP monitoring is a key tenet of neurocritical care, and accounting for zero drift is vital. Intraparenchymal piezoelectric strain gauge sensors are commonly implanted to monitor ICP. Laboratory bench testing results can differ from in vivo observations, revealing the shortcomings of current ICP sensors.

Development of normal pressure hydrocephalus following post-traumatic external hydrocephalus in an adult patient.

We report the case of 74-year-old patient suspected of post-traumatic external hydrocephalus (EH) following a mild traumatic brain injury with a progressive neurological decline and a concomitant enlargement of subarachnoid spaces without ventriculomegaly on CT scan. A lumbar puncture revealed raised ICP and a careful CSF withdrawal was performed, resulting in an immediate neurological improvement, confirming the diagnosis of EH. During the 20-month follow-up, the patient presented progressive signs of normal pressure hydrocephalus (NPH): gait and cognitive decline, ventriculomegaly and the lumbar infusion study confirmed disturbed CSF dynamics. The patient underwent a ventriculoperitoneal shunt surgery, resulting in a long-lasting improvement.

Is Lumbar Puncture Needed? - Noninvasive Assessment of ICP Facilitates Decision Making in Patients with Suspected Idiopathic Intracranial Hypertension.

PURPOSE: Idiopathic intracranial hypertension (IIH) usually occurs in obese women of childbearing age. Typical symptoms are headache and sight impairment. Lumbar puncture (LP) is routinely used for both diagnosis and therapy (via cerebrospinal fluid drainage) of IIH. In this study, noninvasively assessed intracranial pressure (nICP) was compared to LP pressure (LPP) in order to clarify its feasibility for the diagnosis of IIH. MATERIALS AND METHODS: nICP was calculated using continuous signals of arterial blood pressure and cerebral blood flow velocity in the middle cerebral artery, a method which has been introduced recently. In 26 patients (f = 24, m = 2; age: 33 ±â€Š11 years), nICP was assessed one hour prior to LPP. If LPP was > 20 cmH2O, lumbar drainage was performed, LPP was measured again, and also nICP was reassessed. RESULTS: In total, LPP and nICP correlated with R = 0.85 (p < 0.001; N = 38). The mean difference of nICP-LPP was 0.45 ±â€Š4.93 cmH2O. The capability of nICP to diagnose increased LPP (LPP > 20 cmH2O) was assessed by ROC analysis. The optimal cutoff for nICP was close to 20 cmH2O with both a sensitivity and specificity of 0.92. Presuming 20 cmH2O as a critical threshold for the indication of lumbar drainage, the clinical implications would coincide in both methods in 35 of 38 cases. CONCLUSION: The TCD-based nICP assessment seems to be suitable for a pre-diagnosis of increased LPP and might eliminated the need for painful lumbar puncture if low nICP is detected.

Global Neurocognitive and Frontal Functions Analysis and Precision Intrathecal Pressure Measurement to Settle the Diagnostic Dilemma of the Normal Pressure Hydrocephalus: A Preliminary Experience.

INTRODUCTION: Normal-pressure hydrocephalus (NPH) is a common condition associated with a cognitive deterioration and possibly involving up to 9%-14% of all nursing home residents older than 65 years old. The purpose of the present paper is to introduce an inclusive study protocol aimed at increasing the diagnostic precision and follow-up accuracy. METHODS: A total of 28 patients were operated on for NPH in our institution in the period ranging between January 2015 and December 2019. All the patients underwent magnetic resonance imaging of the brain with standard sequences, calculation of the Evans index and corpus callosum angle, and evaluations by means of Montreal Cognitive Assessment (MOCA), Mini-Mental State Examination, and Frontal Assessment Battery (FAB) neuropsychological tests preoperatively and at 1 and 6 months. A preoperative lumbar test infusion (LIT) with fine measurement of the intrathecal pressures at the beginning and at the end of the procedures was performed. RESULTS: MOCA and FAB proved an overall improvement of the neurocognitive conditions at 1 month postoperatively. The mean pressure at the beginning of the LIT, was negatively associated with the neuropsychological outcome variables (Mini-Mental State Examination, FAB, and MOCA) in the 3 different evaluations, with FAB and MOCA at 6 months. We found a strong positive correlation between the Evans index as measured on the first magnetic resonance imaging scan both with the diastolic and systolic pressure at the beginning of the test. CONCLUSIONS: Neuropsychological assessment, combined with LIT with intrathecal pressure managements aids the diagnostic process in patients affected by NPH. It allows standardizing in a rigorous fashion the follow-up evaluation of patients undergoing surgery for a ventriculoperitoneal shunt.

Diffusion Tensor Imaging Profiles Can Distinguish Diffusivity and Neural Properties of White Matter Injury in Hydrocephalus vs. Non-hydrocephalus Using a Strategy of a Periodic Table of DTI Elements.

Background: The aim of this study was to create a simplistic taxonomy to improve transparency and consistency in, and reduce complexity of, interpreting diffusion tensor imaging (DTI) profiles in white matter disruption. Using a novel strategy of a periodic table of DTI elements, we examined if DTI profiles could demonstrate neural properties of disruption sufficient to characterize white matter changes specific for hydrocephalus vs. non-hydrocephalus, and to distinguish between cohorts of neural injury by their differing potential for reversibility. Methods: DTI datasets from three clinical cohorts representing pathological milestones from reversible to irreversible brain injury were compared to those of healthy controls at baseline, over time and with interventions. The final dataset comprised patients vs. controls in the following groupings: mild traumatic brain injury (mTBI), n = 24 vs. 27, normal pressure hydrocephalus (NPH), n = 16 vs. 9 and Alzheimer's disease (AD), n = 27 vs. 47. We generated DTI profiles from fractional anisotropy (FA) and mean, axial and radial diffusivity measures (MD, L1 and L2 and 3 respectively), and constructed an algorithm to map changes consistently to a periodic table of elements, which fully described their diffusivity and neural properties. Results: Mapping tissue signatures to a periodic table of DTI elements rapidly characterized cohorts by their differing patterns of injury. At baseline, patients with mTBI displayed the most preserved tracts. In NPH, the magnitude of changes was dependent on "familial" DTI neuroanatomy, i.e., potential for neural distortion from risk of ventriculomegaly. With time, patients with Alzheimer's disease were significantly different to controls across multiple measures. By contrast, patients with mTBI showed both loss of integrity and pathophysiological processes of neural repair. In NPH, some patterns of injury, such as "stretch/compression" and "compression" were more reversible following intervention than others; these neural profile properties suggested "microstructural resilience" to injury. Conclusion: Using the novel strategy of a periodic table of DTI elements, our study has demonstrated it is possible to distinguish between different cohorts along the spectrum of brain injury by describing neural profile properties of white matter disruption. Further work to contribute datasets of disease toward this proposed taxonomic framework would enhance the translatability of DTI profiles to the clinical-research interface.

Clinical Outcomes After Ventriculo-Peritoneal Shunting in Patients With Classic vs. Complex NPH.

Objective: Normal pressure hydrocephalus (NPH) is a neurological condition characterized by a clinical triad of gait disturbance, cognitive impairment, and urinary incontinence in conjunction with ventriculomegaly. Other neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and vascular dementia share some overlapping clinical features. However, there is evidence that patients with comorbid NPH and Alzheimer's or Parkinson's disease may still exhibit good clinical response after CSF diversion. This study aims to evaluate clinical responses after ventriculo-peritoneal shunt (VPS) in a cohort of patients with coexisting NPH and neurodegenerative disease. Methods: The study has two components; (i) a pilot study was performed that specifically focused upon patients with Complex NPH and following the inclusion of the Complex NPH subtype into consideration for the clinical NPH programme, (ii) a retrospective snapshot study was performed to confirm and characterize differences between Classic and Complex NPH patients being seen consecutively over the course of 1 year within a working subspecialist NPH clinic. We studied the characteristics of patients with Complex NPH, utilizing clinical risk stratification and multimodal biomarkers. Results: There was no significant difference between responders and non-responders to CSF diversion on comorbidity scales. After VPS insertion, significantly more Classic NPH patients had improved cognition compared to Complex NPH patients (p = 0.005). Improvement in gait and urinary symptoms did not differ between the groups. 26% of the Classic NPH group showed global improvement of the triad, and 42% improved in two domains. Although only 8% showed global improvement of the triad, all Complex NPH patients improved in gait. Conclusions: Our study has demonstrated that the presence of neurodegenerative disorders co-existing with NPH should not be the sole barrier to the consideration of high-volume tap test or lumbar drainage via a specialist NPH programme. Further characterization of distinct cohorts of NPH with differing degrees of CSF responsiveness due to overlay from neurodegenerative or comorbidity risk burden may aid toward more precise prognostication and treatment strategies. We propose a simplistic conceptual framework to describe NPH by its Classic vs. Complex subtypes to promote the clinical paradigm shift toward subspecialist geriatric neurosurgery by addressing needs for rapid screening tools at the clinical-research interface.

Hydrocephalus and the neuro-intensivist: CSF hydrodynamics at the bedside.

Hydrocephalus (HCP) is far more complicated than a simple disorder of cerebrospinal fluid (CSF) circulation. HCP is a common complication in patients with subarachnoid hemorrhage (SAH) and after craniectomy. Clinical measurement in HCP is mainly related to intracranial pressure (ICP) and cerebral blood flow. The ability to obtain quantitative variables that describe CSF dynamics at the bedside before potential shunting may support clinical intuition with a description of CSF dysfunction and differentiation between normal pressure hydrocephalus and brain atrophy. This review discusses the advanced research on HCP and how CSF is generated, stored and absorbed within the context of a mathematical model developed by Marmarou. Then, we proceed to explain the main quantification analysis of CSF dynamics using infusion techniques for deciding on definitive treatment. We consider that such descriptions of multiple parameters of measurements need to be significantly appreciated by the caring neuro-intensivist, for better understanding of the complex pathophysiology and clinical management and finally, improve of the prognosis of these patients with HCP.

Peak appearance time in pulse waveforms of intracranial pressure and cerebral blood flow velocity.

The shape of the pulse waveforms of intracranial pressure (ICP) and cerebral blood flow velocity (CBFV) typically contains three characteristic peaks. It was reported that alterations in cerebral hemodynamics may influence the shape of the pulse waveforms by changing peaks' configuration. However, the changes in peak appearance time (PAT) in ICP and CBFV pulses are only described superficially. We analyzed retrospectively ICP and CBFV signals recorded in traumatic brain injury patients during decrease in ICP induced by hypocapnia (n = 11) and rise in ICP during episodes of ICP plateau waves (n = 8). All three peaks were manually annotated in over 48 thousand individual pulses. The changes in PAT were compared between periods of vasoconstriction (expected during hypocapnia) and vasodilation (expected during ICP plateau waves) and their corresponding baselines. Correlation coefficient (rS) analysis between mean ICP and mean PATs was performed in each individual recording. Vasodilation prolonged PAT of the first peaks of ICP and CBFV pulses and the third peak of CBFV pulse. It also accelerated PAT of the third peak of ICP pulse. In contrast, vasoconstriction shortened appearance time of the first peaks of ICP and CBFV pulses and the second peak of ICP pulses. Analysis of individual recordings demonstrated positive association between changes in PAT of all three peaks in the CBFV pulse and mean ICP (rS range: 0.32-0.79 for significant correlations). Further study is needed to test whether PAT of the CBFV pulse may serve as an indicator of changes in ICP-this may open a perspective for non-invasive monitoring of alterations in mean ICP.

Analysis of relative changes in pulse shapes of intracranial pressure and cerebral blood flow velocity.

Objective.Analysis of relative changes in the shapes of pulse waveforms of intracranial pressure (ICP) and transcranial Doppler cerebral blood flow velocity (CBFV) may provide information on intracranial compliance. We tested this hypothesis, introducing an index named the ratio of pulse slopes (RPS) that is based on inclinations of the ascending parts of the ICP and CBFV pulse waveforms. It has hypothetically a simple interpretation: a value of 1 indicates good compliance and a value less than 1, reduced compliance. Here, we investigated the usefulness of RPS for assessment of intracranial compliance.Approach.ICP and CBFV signals recorded simultaneously in 30 normal-pressure hydrocephalus patients during infusion tests were retrospectively analysed. CBFV was measured in the middle cerebral artery. Changes in RPS during the test were compared with changes in the height ratio of the first and second peak of the ICP pulse (P1/P2) and the shape of the ICP pulse was classified from normal (1) to pathological (4). Values are medians (lower, upper quartiles).Main results.There was a significant correlation between baseline RPS and intracranial elasticity (R = -0.55,p = 0.0018). During the infusion tests, both RPS and P1/P2 decreased with rising ICP [RPS, 0.80 (0.56, 0.92) versus 0.63 (0.44, 0.80),p = 0.00015; P1/P2, 0.58 (0.50, 0.91) versus 0.52 (0.36, 0.71),p = 0.00009] while the ICP pulses became more pathological in shape [class: 3 (2, 3) versus 3 (3, 4),p = 0.04]. The magnitude of the decrease in RPS during infusion was inversely correlated with baseline P1/P2 (R = -0.40,p < 0.03).Significance.During infusion, the slopes of the ascending parts of ICP and CBFV pulses become increasingly divergent with a shift in opposite directions. RPS seems to be a promising methodological tool for monitoring intracranial compliance with no additional volumetric manipulation required.

Causal relationship between slow waves of arterial, intracranial pressures and blood velocity in brain.

PURPOSE: Slow vasogenic waves in arterial blood pressure (ABP), intracranial pressure (ICP) and cerebral blood flow velocity (FV) carry information on multiple brain homeostatic control mechanisms. This work presents an approach to evaluate causal relation between oscillatory modes of these signals as an alternative to time or frequency domain Granger analysis. METHODS: Forty-five patients with simultaneous recordings of ICP, ABP and FV during CSF infusion studies were examined retrospectively. Each time series was decomposed into ten intrinsic mode functions (IMFs) via Ensemble Empirical Mode Decomposition (EEMD) and, afterwards, Granger causality (GC) was computed. RESULTS: Slow waves of ICP, ABP and FV were reconstructed from mode functions IMF6-9 of each time series, covering a frequency range between 0.013 and 0.155 Hz. Most significant connections were from FV to ICP, being stronger during elevation of mean ICP during infusion study. No G-causality was found between any of the IMFs during the baseline phase. CONCLUSION: Nonlinearity and nonstationarity of the cerebral and systemic signals can be addressed using EEMD decomposition There is a causal influence of slow waves of FV on slow waves on ICP during the plateau phase of the infusion study for a frequency band between 0.095 and 0.155 Hz. This relationship is magnified during mild intracranial hypertension.

CSF Dynamics for Shunt Prognostication and Revision in Normal Pressure Hydrocephalus.

BACKGROUND: Despite the quantitative information derived from testing of the CSF circulation, there is still no consensus on what the best approach could be in defining criteria for shunting and predicting response to CSF diversion in normal pressure hydrocephalus (NPH). OBJECTIVE: We aimed to review the lessons learned from assessment of CSF dynamics in our center and summarize our findings to date. We have focused on reporting the objective perspective of CSF dynamics testing, without further inferences to individual patient management. DISCUSSION: No single parameter from the CSF infusion study has so far been able to serve as an unquestionable outcome predictor. Resistance to CSF outflow (Rout) is an important biological marker of CSF circulation. It should not, however, be used as a single predictor for improvement after shunting. Testing of CSF dynamics provides information on hydrodynamic properties of the cerebrospinal compartment: the system which is being modified by a shunt. Our experience of nearly 30 years of studying CSF dynamics in patients requiring shunting and/or shunt revision, combined with all the recent progress made in producing evidence on the clinical utility of CSF dynamics, has led to reconsidering the relationship between CSF circulation testing and clinical improvement. CONCLUSIONS: Despite many open questions and limitations, testing of CSF dynamics provides unique perspectives for the clinician. We have found value in understanding shunt function and potentially shunt response through shunt testing in vivo. In the absence of infusion tests, further methods that provide a clear description of the pre and post-shunting CSF circulation, and potentially cerebral blood flow, should be developed and adapted to the bed-space.

External Hydrocephalus After Traumatic Brain Injury: Retrospective Study of 102 Patients.

INTRODUCTION: External hydrocephalus (EH) refers to impairment of extra-axial cerebrospinal fluid flow with enlargement of the subarachnoid space (SAS) and concomitant raised intracranial pressure (ICP). It is often confused with a subdural hygroma and overlooked, particularly when there is no ventricular enlargement. In this study, we aimed to describe the epidemiology of EH in a large population of adults with traumatic brain injury (TBI). METHODS: This observational, retrospective cohort study was conducted in adult patients who were admitted with TBI to the Department of Clinical Neuroscience at Addenbrooke's Hospital (Cambridge, UK) over a period of 3 years (2014-2017). Patients were included in the study if they had ICP monitoring and at least three CT scans within the first 21 days to assess SAS evolution. Patients who underwent a decompressive craniectomy were excluded. SAS was assessed individually on each CT scan by two independent investigators. ICP data were analysed with ICM+ software (Cambridge Enterprise Ltd., Cambridge, UK). Short-term and 6-month outcomes were examined. The groups of patients with and without EH were compared. RESULTS: Of the 102 patients included in the study, 30.4% developed EH after a delay of 2.98 ± 2.4 days. The initial Glasgow Coma Scale (GCS) scores did not differ between patients with and without EH. Subarachnoid haemorrhage was found to be the main risk factor for EH. Patients with EH required a significantly longer period of mechanical ventilation (+6.9 days), were more likely to have a tracheostomy (55% versus 33%), and had a longer stay in the intensive care unit (+8.5 days). ICP was higher during the 48 h after diagnosis of EH than during the previous 48 h. EH survivors had a lower mean Glasgow Outcome Scale Extended (GOS-E) score (4.6 versus 5.9, P = 0.031) and were more likely to receive a permanent shunt for secondary hydrocephalus (17.4% versus 1.8%, odds ratio 7.1). CONCLUSION: In adults with TBI, EH remains insufficiently understood and probably underdiagnosed. This study showed that it is a frequent complication of TBI, with significant clinical consequences.