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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.

Purpose Accurate diagnosis of Pseudotumor Cerebri Syndrome (PTCS) in children is challenging. We aimed to see if the clinical and radiological assessment that is carried out before lumbar puncture could predict subsequently recorded CSF pressures, and thus whether it could be used to increase diagnostic certainty of paediatric PTCS. Methods We used internationally recognised diagnostic criteria to derive a list of clinical, brain neuroimaging and venography features that were accepted to be associated with a diagnosis of PTCS. We performed a retrospective cohort study of children referred to our centre with suspected PTCS, identifying the presence or absence of those features for each child at initial presentation. The sum total scores of the features that were present were correlated with the child���s recorded CSF pressure. Results The sum total scores were significantly positively correlated with recorded CSF pressures. The positive correlation was seen when clinical and brain neuroimaging features were included alone, and the correlation was slightly stronger when venography features were included in addition. Conclusion Calculating the sum total of clinical, brain neuroimaging and venography features (where venography is performed) present at initial presentation can help in the management of children under investigation for PTCS. Children with high scores are more likely to have severely raised CSF pressures and thus may warrant more urgent LP investigations. By contrast, in children with subtle abnormalities in optic disc appearance such that disc oedema cannot be ruled out, a low score may add further reassurance and less urgency to proceed to LP., nil

Funder: University of Cambridge, Objectives: The diagnosis of shunt malfunction is often not straightforward. We have explored, in symptomatic shunted patients with hydrocephalus or pseudotumour cerebri syndrome (PTCS), the accuracy of CSF infusion tests in differentiating a functioning shunt from one with possible problems, and the health economic consequences. Methods: Participants: hydrocephalus/PTCS patients with infusion tests performed from January 2013 until December 2015. We followed patients up after 6 and 12 months from the test to determine whether they had improved, had persisting symptoms or had required urgent revision. We calculated the total cost savings of revision versus infusion tests and standard protocol of revision and ICP monitoring versus infusion tests. Results: Three hundred sixty-five shunt infusion tests had been performed where a shunt prechamber/reservoir was present. For hydrocephalus patients, more than half of the tests (~ 55%, 155 out of 280) showed no shunt malfunction versus 125 with possible malfunction (ages 4 months to 90 years old). For PTCS patients aged 10 to 77 years old, 47 had possible problems and 38 no indication for shunt malfunction. Overall, > 290 unnecessary revisions were avoided over 3 years’ time. Two hundred fifty-eight (> 85%) of those non-surgically managed, remained well, did not deteriorate and did not require surgery. No infections were associated with infusion studies. For Cambridge, the overall savings from avoiding revisions was £945,415 annually. Conclusions: Our results provide evidence of the importance of shunt testing in vivo to confirm shunt malfunction. Avoiding unnecessary shunt revisions carries a strong health benefit for patients that also translates to a significant financial benefit for the National Health Service and potentially for other healthcare systems worldwide.

Funder: University of Cambridge, Objective: Pseudotumour cerebri syndrome (PTCS including idiopathic intracranial hypertension) is characterised by the symptoms and signs of raised cerebrospinal fluid pressure (CSFp) in the absence of ventricular dilatation or an intracranial mass lesion. Its aetiology is unknown in the majority of cases but there is much evidence for impaired CSF absorption. Traditionally, sagittal sinus pressure has been considered to be independent of CSF pressure in adults. However, the discovery of stenoses of intracranial venous sinuses and introduction of venous sinus stenting has highlighted the importance of the venous drainage in PTCS. In this study, we have explored the relationship between CSFp and SSp before and during a CSF infusion test and during CSF drainage. Materials and methods: Ten patients (9 females:1 male) with PTCS underwent infusion studies in parallel with direct retrograde cerebral venography. Both SSp and CSFp were recorded at a baseline and during CSFp elevation in a course of a CSF infusion test. The drainage of CSF after the CSF infusion was performed in 7 patients. In 5 cases, jugular venous pressure was also measured. Results: CSFp and SSp including their amplitudes correlated significantly and strongly both at baseline (R = 0.96; p = 0.001) and during infusion (R = 0.92; p = 0.0026). During drainage, this correlation was maintained until SSp reached a stable value, whereas CSFp continued to decrease. Conclusions: In this series of ten patients with PTCS, CSFp and SSp were coupled, both at baseline and during infusion. The implications of such coupling for the calculation of CSF outflow resistance are discussed.

Funder: University of Cambridge, Purpose: There is a growing body of evidence highlighting the importance of comprehensive intracranial pressure (ICP) values in pseudotumor cerebri syndrome (PTCS). Due to the highly dynamic nature of ICP, several methods of ICP monitoring have been established, including the CSF infusion study. We have performed a retrospective review of the CSF dynamics measurements for all pediatric patients investigated for PTCS in our center and examined their diagnostic value compared with clinical classification. Methods: We retrospectively recruited 31 patients under 16 years of age investigated for PTCS by CSF infusion test. We used the clinically provided Friedman classification 13/31 patients with definite PTCS (group A), 13/31 with probable PTCS (group B), and 5/31 not PTCS (group C), to compare CSF dynamics in the 3 groups. Results: CSF pressure (CSFp) was significantly increased in group A (29.18 ± 7.72 mmHg) compared with B (15.31 ± 3.47 mmHg; p = 1.644e-05) and C (17.51 ± 5.87; p = 0.01368). The amplitude (AMP) was higher in the definite (2.18 ± 2.06 mmHg) than in group B (0.68 ± 0.37; p = 0.01382). There was no in either CSFp or AMP between groups B and C. No lower breakpoint of the AMP-P line was observed in group A but was present in 2/13 and 2/5 patients in groups B and C. In group A, sagittal sinus pressure (SSp) and elasticity were the only parameters above threshold (p = 4.2e-06 and p = 0.001953, respectively), In group B, only the elasticity was significantly higher than the threshold (p = 004257). Group C did not have any of the parameters raised. The AUC of CSFp, elasticity, and SSp for the 3 groups was 93.8% (84.8–100% CI). Conclusions: Monitoring of CSFp and its dynamics, besides providing a more precise methodology for measuring CSFp, could yield information on the dynamic parameters of CSFp that cannot be derived from CSFp as a number, accurately differentiating between the clinically and radiologically derived entities of PTCS.

Background Cerebral vasospasm (VS) and delayed cerebral ischemia (DCI) constitute major complications following subarachnoid hemorrhage (SAH). A few studies have examined the relationship between different indices of cerebrovascular dynamics with the occurrence of VS. However, their potential association with the development of DCI remains elusive. In this study, we investigated the pattern of changes of different transcranial Doppler (TCD)-derived indices of cerebrovascular dynamics during vasospasm in patients suffering from subarachnoid hemorrhage, dichotomized by the presence of delayed cerebral ischemia. Methods A retrospective analysis was performed using recordings from 32 SAH patients, diagnosed with VS. Patients were divided in two groups, depending on development of DCI. Magnitude of slow waves (SWs) of cerebral blood flow velocity (CBFV) was measured. Cerebral autoregulation was estimated using the moving correlation coefficient Mxa. Cerebral arterial time constant (tau) was expressed as the product of resistance and compliance. Complexity of CBFV was estimated through measurement of sample entropy (SampEn). Results In the whole population (N = 32), magnitude of SWs of ipsilateral to VS side CBFV was higher during vasospasm (4.15 ± 1.55 vs before: 2.86 ± 1.21 cm/s, p N = 19, p p = 0.02). Vasospasm caused a non-significant shortening of ipsilateral values of tau and increase in SampEn in all patients related to pre-VS measurements, as well as an insignificant increase of Mxa in DCI related to non-DCI group (N = 13). Conclusions In patients suffering from subarachnoid hemorrhage, TCD-detected VS was associated with higher ipsilateral CBFV SWs, related to pre-VS measurements. Higher CBFV SWs before VS were significantly predictive of delayed cerebral ischemia.

The dynamic relationship between pulse waveform of intracranial pressure (ICP) and transcranial Doppler (TCD) cerebral blood flow velocity (CBFV) may contain information about cerebrospinal compliance. This study investigated the possibility by focusing on the phase shift between fundamental harmonics of CBFV and ICP. Thirty-seven normal pressure hydrocephalus patients (20 men, mean age 58) underwent the cerebrospinal fluid (CSF) infusion tests. The infusion was performed via pre-implanted Ommaya reservoir. The TCD FV was recorded in the middle cerebral artery. Resulting continuous ICP and pressure-volume (PV) signals were analyzed by ICM+ software. In initial stage of the CSF infusion, the phase shift was negative (median value = −11°, range = +60 to −117). There was significant inverse association of phase shift with brain elasticity (R = −0.51; p = 0.0009). In all tests, phase shift consistently decreased during gradual elevation of ICP (p = 0.00001). Magnitude of decrease in phase shift was inversely related to the peak-to-peak amplitude of ICP pulse waveform at a baseline (R = −0.51; p = 0.001). Phase shift between fundamental harmonics of ICP and TCD waveforms decreases during elevation of ICP. This is caused by an increase of time delay between systolic peak of flow velocity wave and ICP pulse.

BACKGROUND: This study aimed to compare four non-invasive intracranial pressure (nICP) methods in a prospective cohort of hydrocephalus patients whose cerebrospinal fluid dynamics was investigated using infusion tests involving controllable test-rise of ICP. METHOD: Cerebral blood flow velocity (FV), ICP and non-invasive arterial blood pressure (ABP) were recorded in 53 patients diagnosed for hydrocephalus. Non-invasive ICP methods were based on: (1) interaction between FV and ABP using black-box model (nICP_BB); (2) diastolic FV (nICP_FVd); (3) critical closing pressure (nICP_CrCP); (4) transcranial Doppler-derived pulsatility index (nICP_PI). Correlation between rise in ICP (∆ICP) and ∆nICP and averaged correlations for changes in time between ICP and nICP during infusion test were investigated. RESULTS: From baseline to plateau, all nICP estimators increased significantly. Correlations between ∆ICP and ∆nICP were better represented by nICP_PI and nICP_BB: 0.45 and 0.30 (p

Cerebral autoregulation assessed using transcranial Doppler (TCD) mean flow velocity (FV) in response to various physiological challenges is predictive of outcome after traumatic brain injury (TBI). Systolic and diastolic FV have been explored in other diseases. This study aims to evaluate the systolic, mean and diastolic FV for monitoring autoregulation and predicting outcome after TBI.300 head-injured patients with blood pressure (ABP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), and FV recordings were studied. Autoregulation was calculated as a correlation of slow changes in diastolic, mean and systolic components of FV with CPP (Dx, Mx, Sx, respectively) and ABP (Dxa, Mxa, Sxa, respectively) from 30 consecutive 10 s averaged values. The relationship with age, severity of injury, and dichotomized 6 months outcome was examined.Association with outcome was significant for Mx and Sx. For favorable/unfavorable and death/survival outcomes Sx showed the strongest association (F = 20.11; P = 0.00001 and F = 13.10; P = 0.0003, respectively). Similarly, indices derived from ABP demonstrated the highest discriminatory value when systolic FV was used (F = 12.49; P = 0.0005 and F = 5.32; P = 0.02, respectively). Indices derived from diastolic FV demonstrated significant differences (when calculated using CPP) only when comparing between fatal and non-fatal outcome.Systolic flow indices (Sx and Sxa) demonstrated a stronger association with outcome than the mean flow indices (Mx and Mxa), irrespective of whether CPP or ABP was used for calculation.

Increased slow-wave activity in intracranial pressure (ICP) signifies an exhausted cerebrospinal compensatory reserve across a range of conditions. In this study, we attempted to describe synchronisation between slow waves of ICP and of near-infrared spectroscopy (NIRS) variables during controlled elevation of ICP. Nineteen patients presenting with symptomatic hydrocephalus underwent a Computerised Infusion Test. NIRS-derived indices, ICP and arterial blood pressure (ABP) were recorded simultaneously. ICP increased from 9.3 (6.0) mmHg to a 17.1 (8.9) mmHg during infusion. Slow waves in ICP were accompanied by concurrent waves in each NIRS variable (including deoxygenated haemoglobin (Hb) and oxygenated haemoglobin (HbO2)) with a mean coherence of >0.7 and no significant phase shift. In the same bandwidth (0.3–1.8 min−1), ABP fluctuations occurred with a coherence of 0.77 and phase lead of 40° with respect to ICP. The power of ICP slow waves increased significantly during infusion plateau with a corresponding increase in power of Hb waves. Slow fluctuations in cerebral oximetry as detected by NIRS coincide with and are implicated in the origin of ICP slow waves and increases during periods of exhausted cerebrospinal compensatory reserve. NIRS may be used as a non-invasive marker of increased ICP slow waves (and therefore reduced CSF compensatory reserve).

Objective The strict relationship between shunt-responsiveness and increased resistance to CSF outflow (Rout) as reported in 1981 by Borgensen and Gjerris [1] was later presented as significant but not strong in the‘Dutch NPH’ trial [2] and recently reported as unconvincing in the ‘European NPH study’ [3]. We reviewed our ongoing database to study the relationship between parameters describing CSF circulation and pressure-volume compensation with clinical improvement after shunting.

Background Transcranial Doppler (TCD) based methods have been used to estimate ICP noninvasively (nICP), however their relative accuracy varies between different types of intracranial hypertension: vasogenic, CSF circulatory or secondary to brain volumetric changes (oedema, contusion, hematoma, etc). This study aimed to compare four nICP methods in a prospective cohort of hydrocephalus patients whose CSF dynamics was investigated using infusion tests involving controllable test-rise of ICP.

16 models of valves, currently in use in the U.K., have been tested long-term in the U.K. Shunt Evaluation Laboratory according to the protocol based on the new ISO 7197 standard. Valves tested were: Medtronic PS Medical: Delta Valve, Flow Control and Lumbo-Peritoneal Shunt Heyer-Schulte Nero-Care: In-line, Low Profile and Pudenz Flushing Valve Codman: Codman-Hakim Programmable, Hakim Precision, Accu-Flo, Holter, Uni-Shunt, and siphon-preventing device – SiphonGuard NMT: Orbis-Sigma Valve, Omni-Shunt and Hakim Valve Sophysa: Sophy Programmable Valve Radionics: Contour-Flex Valve. The majority of the valves had a non-physiologically low hydrodynamic resistance (with the exception of Orbis-Sigma, PS Lumbo-Peritoneal and Heyer-Schulte In-Line). This may result in overdrainage both related to posture and during nocturnal cerebral vasogenic waves. A long distal catheter increases the resistance of these valves by 100–200%. Drainage through valves without siphon-preventing mechanism is very sensitive to body posture. This may produce grossly negative intracranial pressure after implantation. A few shunts (Delta, Low Profile and Pudenz-Flushing with Anti-Siphon Devices) offer a reasonable resistance to negative outlet pressure, and hence potentially might prevent complications related to overdrainage. On the other hand, valves with siphon-preventing devices may be blocked by raised subcutaneous pressure (exception: SiphonGuard, but this device may block the drainage because of its faulty design). In most of the silicone-diaphragm valves, closing pressure varied and reached values lower than that specified by the manufacturer (exception: Heyer-Schulte Pudenz Flushing Valve). All programmable valves are susceptible to overdrainage in the upright body position. Programmed settings may be changed by external magnetic fields. Most shunts are very sensitive to the presence of small particles in the drained fluid. The behavior of a valve revealed during such testing is of immediate relevance to the surgeon and may not be adequately described in the manufacturer's product information. These results are also relevant to the assessment of shunt function in-vivo using an infusion test.

Background It has been reported that pumping a shunt in situ may precipitate a proximal occlusion, and/or lead to ventricular over-drainage, particularly in the context of small ventricles. In the laboratory we measured the effect of pumping the pre-chamber of hydrocephalus shunts on intracranial hypotension. Materials and methods A simple physical model of the CSF space in a hydrocephalic patient was constructed with appropriate compliance, CSF production and circulation. This was used to test eleven different hydrocephalus shunts. The lowest pressure obtained, the number of pumps needed to reach this pressure, and the maximum pressure change with a single pump, were recorded. Results All models were able to produce negative pressures ranging from -11.5 mmHg (Orbis-Sigma valve) to -233.1 mmHg (Sinu-Shunt). The number of pumps required reaching these levels ranged from 21 (PS Medical LP Reservoir) to 315 (Codman Hakim-Programmable). The maximum pressure change per pump ranged from 0.39 mmHg (Orbis-Sigma valve) to 23.1 (PS Medical LP Reservoir). Conclusion Patients, carers and professionals should be warned that 'pumping' a shunt's pre-chamber may cause a large change in intracranial pressure and predispose the patient to ventricular catheter obstruction or other complications.

Background Adjustable shunts are very popular in the management of hydrocephalus and are believed to help in minimizing the number of surgical revisions. The drawback with almost all constructions is that they may be accidentally readjusted in relatively weak magnetic fields (around 30–40 mTesla) Materials and methods The ProGav Miethke shunt is composed of an adjustable ballon-spring valve unit and an integrated over-drainage compensating gravitational device (known as the shunt assistant). A mechanical 'brake' is intended to prevent changes to the valve's performance level in a strong magnetic field. We evaluated the performance and hydrodynamic properties of a sample of three valves in the UK Shunt Evaluation Laboratory. Results All the shunts showed good mechanical durability over the three-month period of testing, and good stability of hydrodynamic performance over a one-month period The pressure-flow performance curves, operating, opening and closing pressures fell within the limits specified by the manufacturer, and changed according to the programmed performance levels. The operating pressure increased when the shunt assistant was in the vertical position, as specified. The valve has a low hydrodynamic resistance (0.53 mm mmHg ml-1 min-1). External programming proved to be easy and reliable. Strong magnetic fields from a 3 Tesla MR scanner were not able to change the programming of the valve. Conclusion The ProGAV shunt is an adjustable, low resistance valve that is able to limit posture-related over-drainage. Unlike other adjustable valves, the ProGAV cannot be accidentally re-adjusted by external magnetic field such as a 3T MR scanner.

Background Cerebrospinal Fluid (CSF) pressure-volume compensatory parameters may change over time under pathological and normal circumstances. Normal ageing may affect CSF compensation: the resistance to CSF outflow increases and the formation of CSF decreases with age. In acute hydrocephalus after subarachnoid haemorrhage, baseline intracranial pressure (ICP) and resistance to CSF outflow acutely increase but they may return towards baseline over the next few weeks. Idiopathic Normal Pressure Hydrocephalus (iNPH) awaits longitudinal studies. Is NPH always the late (compensated) stage of acute hydrocephalus? Are the CSF compensatory parameters invariant in time (counting from the onset of clinical symptoms) or do they change with time?

Materials and Methods Ten patients with idiopathic NPH (mean age 69 years) underwent a CSF infusion study via a previously implanted right frontal ventricular catheter connected to a subcutaneous reservoir. CBF was measured by H215O PET at baseline and then during the steady-state plateau of raised ICP. The PET images were co-registered to 3D structural T1-weighted MR images. In 10 healthy normal volunteers (mean age 45 years) image acquisition and reconstruction were accomplished in the same manner, except that only a baseline CBF determination was performed.