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.

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.

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.

Shunt infusion studies: impact on patient outcome, including health economics.

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.

Ventriculo-peritoneal shunting is a safe and effective treatment for idiopathic intracranial hypertension.

PURPOSE: To determine the outcome of ventriculo-peritoneal shunts as a treatment for idiopathic intracranial hypertension (IIH) Materials and Methods: Retrospective case series of 28 patients with IIH and evidence of raised intracranial pressure (ICP) who underwent shunt insertion. Patients were identified from a prospectively updated operative database. A case-notes review was performed and data on type of shunt, pre- and post-operative symptoms, ophthalmological findings and post-operative complications were recorded. RESULTS: All patients had symptoms of IIH that had failed medical management. Twelve patients had previous lumbo-peritoneal shunts and 2 patients had previous venous sinus stents. All patients had evidence of raised ICP as papilloedema and raised CSF pressure on lumbar puncture. Twenty-seven patients received a ventriculo-peritoneal shunt and 1 patient a ventriculo-atrial shunt. Twenty-six patients received Orbis Sigma Valves and 2 patients Strata valves. At follow-up all patients (100%) had improvement/resolution of papilloedema, 93% had improved visual acuity and 84% had improved headaches. Mean time to last follow-up was 15 (range 4-96) months. Complications occurred in 3 patients (11%): 2 patients required revision of their peritoneal catheters and 1 patient had an anti-siphon device inserted. CONCLUSIONS: Previous literature reported a ventricular shunt revision rate of 22-42% in the management of IIH. We demonstrate ventriculo-peritoneal shunts to be an effective treatment with a revision rate of 11% compared to the previously reported 22-42%.

Is There a Link Between ICP-Derived Infusion Test Parameters and Outcome After Shunting in Normal Pressure Hydrocephalus?

OBJECTIVE: The term "hydrocephalus" encompasses a range of disorders characterised by clinical symptoms, abnormal brain imaging and derangement of cerebrospinal fluid (CSF) dynamics. The ability to elucidate which patients would benefit from CSF diversion (a shunt or third ventriculostomy) is often unclear. Similar difficulties are encountered in shunted patients to predict the scope for improvement by shunt re-adjustment or revision. MATERIALS AND METHODS: We compared retrospective pre-shunting infusion test results performed in 310 adult patients diagnosed with normal pressure hydrocephalus (NPH) and their improvement after shunting. RESULTS: Resistance to CSF outflow correlated significantly with improvement (p < 0.05). Other markers known from the literature, such as amplitude in CSF pulse pressure, the slope of the amplitude-pressure regression line, or elasticity did not show any correlation with outcome. CONCLUSION: Outcome following shunting in adult NPH is associated with resistance to CSF outflow; however, the latter cannot be taken as an absolute predictor of shunt response.

Validation of Davson's equation in patients suffering from idiopathic normal pressure hydrocephalus.

INTRODUCTION: The so-called Davson's equation relates baseline intracranial pressure (ICP) to resistance to cerebrospinal fluid outflow (Rout), formation of cerebrospinal fluid (If) and sagittal sinus pressure (PSS) There is a controversy over whether this fundamental equation is applicable in patients with normal pressure hydrocephalus (NPH). We investigated the relationship between Rout and ICP and also other compensatory, clinical and demographic parameters in NPH patients. METHOD: We carried out a retrospective study of 229 patients with primary NPH who had undergone constant-rate infusion studies in our hospital. Data was recorded and processed using ICM+ software. Relationships between variables were sought by calculating Pearson product correlation coefficients and p values. RESULTS: We found a significant, albeit weak, relationship between ICP and Rout (R = 0.17, p = 0.0049), Rout and peak-to-peak amplitude of ICP (AMP) (R = 0.27, p = 3.577e-05) and Rout and age (R = 0.16, p = 0.01306). CONCLUSIONS: The relationship found between ICP and Rout provides indirect evidence to support disturbed Cerebrospinal fluid circulation as a key factor in disturbed CSF dynamics in NPH. Weak correlation may indicate that other factors-variable PSS and formation of CSF outflow-contribute heavily to linear model expressed by Davson's equation.

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.

Use of CSF infusion studies to unblock occluded hydrocephalus ventricular shunt catheters: a preliminary report of two patients.

Two patients with ventriculoperitoneal shunts presented with symptoms of raised intracranial pressure indicative of possible shunt malfunction. During investigation, to eliminate this possibility, cerebral spinal fluid infusion studies were performed, which indicated proximal occlusion of the shunts in both cases. Retrograde flush of the ventricular catheter was performed during temporary compression of the siphon-control device, a manoeuvre which blocks distal flow. After the use of this technique, both patients' symptoms improved and they have remained symptom-free for over 2 years. This case report validates the role that infusion studies can play in clearing a blocked ventricular catheter shunt.

Cerebral autoregulation, cerebrospinal fluid outflow resistance, and outcome following cerebrospinal fluid diversion in normal pressure hydrocephalus.

OBJECTIVE: Normal pressure hydrocephalus is not simply the result of a disturbance in CSF circulation, but often includes cardiovascular comorbidity and abnormalities within the cerebral mantle. In this study, the authors have examined the relationship between the global autoregulation pressure reactivity index (PRx), the profile of disturbed CSF circulation and pressure-volume compensation, and their possible effects on outcome after surgery. METHODS: The authors studied a cohort of 131 patients in whom a clinical suspicion of normal pressure hydrocephalus was investigated. Parameters describing CSF compensation and circulation were calculated during the CSF infusion test, and PRx was calculated from CSF pressure and mean arterial blood pressure (MAP) recordings. A simple scale was used to mark the patients' outcome 6 months after surgery (improvement, temporary improvement, and no improvement). RESULTS: The PRx was negatively correlated with resistance to CSF outflow (R = -0.18; p = 0.044); patients with normal CSF circulation tended to have worse autoregulation. The correlation for patients who were surgically treated (n = 83) was R = -0.28; p = 0.01, and it was stronger in patients who experienced sustained improvement after surgery (n = 48, R = -0.43; p = 0.002). In patients who did not improve, the correlation was not significantly different from zero (n = 19, R = -0.07; p = 0.97). There was a trend toward higher values for PRx in nonresponders than in responders (0.16 ± 0.04 vs 0.09 ± 0.02, respectively; p = 0.061), associated with higher MAP values (107.2 ± 8.2 in nonresponders vs 89.5 ± 3.5 in responders; p = 0.195). The product of MAP × (1 + PRx), which was proposed as a measure of combined arterial hypertension and deranged autoregulation, showed a significant association with outcome (greater value in nonresponders; p = 0.013). CONCLUSION: Autoregulation proves to associate with CSF circulation and appears strongest in shunt responders. Outcome following CSF diversion is possibly most favorable when CSF outflow resistance is increased and global cerebral autoregulation is intact, in combination with arterial normotension.