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Aswin Chari, Marek Czosnyka, Hugh K. Richards, John D. Pickard, and Zofia H. Czosnyka

Object

The Cambridge Shunt Evaluation Laboratory was established 20 years ago. This paper summarizes the findings of that laboratory for the clinician.

Methods

Twenty-six models of valves have been tested long-term in the shunt laboratory according to the expanded International Organization for Standardization 7197 standard protocol.

Results

The majority of the valves had a nonphysiologically low hydrodynamic resistance (from 1.5 to 3 mm Hg/[ml/min]), which may result in overdrainage 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 a siphon-preventing mechanism is very sensitive to body posture, which may result in grossly negative intracranial pressure. Siphon-preventing accessories offer a reasonable resistance to negative outlet pressure; however, accessories with membrane devices may be blocked by raised subcutaneous pressure. In adjustable valves, the settings may be changed by external magnetic fields of intensity above 40 mT (exceptions: ProGAV, Polaris, and Certas). Most of the magnetically adjustable valves produce large distortions on MRI studies.

Conclusions

The behavior of a valve revealed during testing is of relevance to the surgeon and may not be adequately described in the manufacturer's product information. The results of shunt testing are helpful in many circumstances, such as the initial choice of shunt and the evaluation of the shunt when its dysfunction is suspected.

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Hugh K. Richards, Helen M. Seeley, and John D. Pickard

Object

In recent years CSF shunt catheters impregnated with rifampicin and clindamycin have been introduced to the United Kingdom (UK) market. These catheters have been shown to be effective in vitro against cultures of Staphylococcus epidermidis. The authors used data collected by the UK Shunt Registry to assess the efficacy of antibiotic-impregnated catheters (AICs) against shunt infection by using a matched-pair study design.

Methods

The UK Shunt Registry contains data on nearly 33,000 CSF shunt-related procedures. The authors identified 1139 procedures in which impregnated catheters had been used, and accurate information was known about diagnosis, number of revisions, sex, and age in these cases. The database was ordered chronologically and searched forward and backward for cases with these same characteristics but involving conventional catheters. Matches were found for 994 procedures.

Results

Among the 994 procedures in which AICs had been used, 30 shunts were subsequently revised because of shunt infection. Among the 994 controls, 47 were subsequently revised for infection (p = 0.048, chi-square test).

Conclusions

The UK Shunt Registry does not collect data on causative organisms, and the surgeon is relied on entirely for the diagnosis of infection. However, with the large number of matched pairs evaluated, the authors attempted to reduce bias to a minimum. Their data suggest that AICs have the potential to significantly reduce shunt infections.

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Ming-Yuan Tseng, Peter J. Hutchinson, Hugh K. Richards, Marek Czosnyka, John D. Pickard, Wendy N. Erber, Stephen Brown, and Peter J. Kirkpatrick

Object

Delayed ischemic deficits (DIDs), a major source of disability following aneurysmal subarachnoid hemorrhage (aSAH), are usually associated with severe cerebral vasospasm and impaired autoregulation. Systemic erythropoietin (EPO) therapy has been demonstrated to have neuroprotective properties acting via EPO receptors on cerebrovascular endothelia and ischemic neurons. In this trial, the authors explored the potential neuroprotective effects of acute EPO therapy following aSAH.

Methods

Within 72 hours of aSAH, 80 patients (age range 24–82 years) were randomized to receive intravenous EPO (30,000 U) or placebo every 48 hours for a total of 90,000 U. Primary end points were the incidence, duration, and severity of vasospasm and impaired autoregulation on transcranial Doppler ultrasonography. Secondary end points were incidence of DIDs and outcome at discharge and at 6 months.

Results

Randomization characteristics were balanced except for age, with the EPO group being older (mean age 59.6 vs 53.3 years, p = 0.034). No differences were demonstrated in the incidence of vasospasm and adverse events; however, patients receiving EPO had a decreased incidence of severe vasospasm from 27.5 to 7.5% (p = 0.037), reduced DIDs with new cerebral infarcts from 40.0 to 7.5% (p = 0.001), a shortened duration of impaired autoregulation (ipsilateral side, p < 0.001), and more favorable outcome at discharge (favorable Glasgow Outcome Scale score, p = 0.039). Among the 71 survivors, the EPO group had fewer deficits measured with National Institutes of Health Stroke Scale (median Score 2 vs 6, p = 0.008).

Conclusions

This preliminary study showed that EPO seemed to reduce delayed cerebral ischemia following aSAH via decreasing severity of vasospasm and shortening impaired autoregulation.

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Andrea Lavinio, Sally Harding, Floor Van Der Boogaard, Marek Czosnyka, Peter Smielewski, Hugh K. Richards, John D. Pickard, and Zofia H. Czosnyka

Object

Exposing patients with ventricular shunts to magnetic fields and MR imaging procedures poses a significant risk of unintentional changes in shunt settings. Shunt valves can also generate considerable imaging artifacts. The purpose of this study was to determine the magnetic field safety and MR imaging compatibility of 5 adjustable models of hydrocephalus shunts.

Methods

The Codman Hakim (regular and with SiphonGuard), Miethke ProGAV, Medtronic Strata, Sophysa Sophy and Polaris programmable valves were tested in a low-intensity magnetic field, and then translational attraction (TA), magnetic torque (MT), and volume of artifacts on T1-weighted spin echo (SE) and gradient echo (GE) pulse sequences in a 3-T MR imaging unit were measured.

Results

The ProGAV and Polaris valves were immune to unintentional reprogramming by magnetic fields up to 3 T. Other valves randomly changed settings, starting from the intensity of field: Sophy valve 24 mT, Strata valve 30 mT, and both Codman Hakim programmable valves from 42 mT. Shunt performances in the 3-T MR imaging unit are reported in the order of compatibility: 1) Codman Hakim regular, TA = 0.005 N, MT = 0.000 Nm, GE = 30 cm3, SE = 2 cm3; 2) Miethke ProGAV, TA = 0.001 N, MT = 1.4 × 10−3 Nm, GE = 231 cm3, SE = 13 cm3; 3) Codman Hakim with SiphonGuard, TA = 0.005 N, MT = 2.3 × 10−3 Nm, GE = 233 cm3, SE = 19 cm3; 4) Medtronic Strata, TA = 0.27 N, MT = 18.0 × 10−3 Nm, GE = 484 cm3, SE = 86 cm3; 5) Sophysa Sophy, TA = 0.82 N, MT = 38.9 × 10−3 Nm, GE = 758 cm3, SE = 72 cm3; and 6) Sophysa Polaris, TA = 0.80 N, MT = 39.6 × 10−3 Nm, GE = 954 cm3, SE = 100 cm3.

Conclusions

All valves, with the exception of the Polaris and ProGAV models, are prone to unintentional reprogramming when exposed to heterogeneous magnetic fields stronger than 40 mT. All tested valves can be considered safe for 3-T MR imaging. All valves generated a distortion of the MR image, especially the GE sequences.

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Peter J. Hutchinson, Mark T. O'Connell, Pippa G. Al-Rawi, Lynn B. Maskell, Rupert Kett-White, Arun K. Gupta, Hugh K. Richards, David B. Hutchinson, Peter J. Kirkpatrick, and John D. Pickard

Object. Clinical microdialysis enables monitoring of the cerebral extracellular chemistry of neurosurgical patients. Introduction of the technique into different hospitals' neurosurgical units has resulted in variations in the method of application. There are several variables to be considered, including length of the catheter membrane, type of perfusion fluid, flow rate of perfusion fluid, and on-line compared with delayed analysis of samples. The objects of this study were as follows: 1) to determine the effects of varying catheter characteristics on substance concentration; 2) to determine the relative recovery and true extracellular concentration by varying the flow rate and extrapolating to zero flow; and 3) to compare substance concentration obtained using a bedside enzyme analyzer with that of off-line high-performance liquid chromatography (HPLC).

Methods. A specially designed bolt was used to conduct two adjacent microdialysis catheters into the frontal cortex of patients with head injury or poor-grade subarachnoid hemorrhage who were receiving ventilation. One reference catheter (10-mm membrane, perfused with Ringer's solution at 0.3 µl/minute) was constant for all studies. The other catheter was varied in terms of membrane length (10 mm or 30 mm), perfusion fluid (Ringer's solution or normal saline), and flow rate (0.1–1.5 µl/minute). The effect of freezing the samples on substance concentration was established by on-line analysis and then repeated analysis after storage at −70°C for 3 months. Samples assayed with the bedside enzyme analyzer were reassessed using HPLC for the determination of glutamate concentrations.

Conclusions. Two adjacent microdialysis catheters that were identical in membrane length, perfusion fluid, and flow rate showed equivalent results. Variations in perfusion fluid and freezing and thawing of samples did not result in differences in substance concentration. Catheter length had a significant impact on substance recovery. Variations in flow rate enabled the relative recovery to be calculated using a modification of the extrapolation-to-zero-flow method. The recovery was approximately 70% at 0.3 µl/minute and 30% at 1 µl/minute (10-mm membrane) for all analytes. Glutamate results obtained with the enzyme analyzer showed good correlation with those from HPLC.

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Marek Czosnyka, Hugh K. Richards, Zofia Czosnyka, Stefan Piechnik, and John D. Pickard

Object. The aim of the study was to assess how cerebrospinal fluid (CSF) pressure—volume compensation depends on cerebrovascular tone.

Methods. In 26 New Zealand White rabbits, intracranial pressure (ICP), arterial blood pressure, and basilar artery blood flow velocity were measured continuously. Saline was infused into the cranial subarachnoid space to assess CSF compensatory parameters: the resistance to CSF outflow, the elastance coefficient, and the amplitude of the ICP pulsatile waveform. Infusions were repeated on two different levels of CO2 concentration in the arterial blood (PaCO2), at normotension and hypotension, and after the death of the animal.

An increase in PaCO2 from a mean of 27 to 48 mm Hg was accompanied by an 18% increase in the resistance to CSF outflow (p < 0.005) and a 64% increase (p < 0.05) in the elastance coefficient. A decrease in arterial blood pressure from a mean of 100 to 51 mm Hg caused a 25% decrease in CSF outflow resistance (p < 0.01) but did not affect the elastance coefficient. Postmortem, a 23% decrease in the CSF outflow resistance was associated with a 102% decrease in the elastance coefficient.

Conclusions. Cerebrovascular parameters have a limited but significant impact on CSF infusion studies. The vascular component of ICP may be identified as a significant factor contributing to this phenomenon. During infusion studies, physiological parameters influencing vascular conditions should be maintained as stable as possible.

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Marek Czosnyka, Hugh K. Richards, Helen E. Whitehouse, and John D. Pickard

✓ Clinical studies with transcranial Doppler suggest that the pulsatility of the flow velocity (FV) waveform increases when the distal cerebrovascular resistance (CVR) increases. To clarify this relationship, the authors studied animal models in which the resistance may be decreased in a controlled manner by an increase in arterial CO2 tension, or by a decrease in cerebral perfusion pressure (CPP) in autoregulating animals. Twelve New Zealand white rabbits were anesthetized, paralyzed, and ventilated. Transcranial Doppler basilar artery FV, laser Doppler cortical blood flow, arterial pressure, intracranial pressure, and end-tidal CO2 concentration were measured continuously. Cerebrovascular resistance (CPP divided by laser Doppler cortical flux) and Gosling Pulsatility Index (PI, defined as an FV pulse amplitude divided by a timed average FV) were calculated as time-dependent variables for each animal.

Four groups of animals undergoing controlled manipulations of CVR were analyzed. In Group I, arterial CO2 concentration was changed gradually from hypocapnia to hypercapnia. In Group II, gradual hemorrhagic hypotension was used to reduce CPP. In Group III, the short-acting ganglion blocking drug trimetaphan was injected intravenously to induce transient hypotension. Intracranial hypertension was produced by subarachnoid saline infusion in Group IV. During the hypercapnic challenge the correlation between the cortical resistance and Doppler flow pulsatility was positive (r = 0.77, p < 0.001). In all three groups in which cerebral perfusion pressure was reduced a negative correlation between pulsatility index and cerebrovascular resistance was found (r = −20.84, p < 0.001). The authors conclude that PI cannot be interpreted simply as an index of CVR in all circumstances.