Comparison of ventricular drain location and infusion test in hydrocephalus.

OBJECTIVES: Suspected cerebrospinal fluid shunt (CSF) dysfunction in hydrocephalic patients poses a diagnostic uncertainty. The clinical picture can be non-specific and CT imaging alone is not always pathognomonic. Infusion tests are an increasingly used investigation for real-time hydrodynamic assessment of shunt patency. We report the correlation between infusion test results with the quality of ventricular drain placement on CT scans in a large retrospective group of hydrocephalic patients. MATERIALS & METHODS: Three hundred and six infusion test results performed in 200 patients were correlated with 306 corresponding CT head scans. Nominal logistic regression was used to correlate shunt catheter position on CT imaging to patency of ventricular drain as determined by infusion tests. RESULTS: Infusion test results of shunt patency are statistically congruent with the analysis of shunt catheter position on CT head scans. Catheter tips completely surrounded by either parenchyma or CSF on CT imaging are strongly associated with evidence of occlusion or patency from infusion tests, respectively (χ² = 51.68, P < 0.0001, n = 306 and χ² = 31.04, P < 0.0001, n = 306). CONCLUSIONS: The most important anatomical factor for shunt patency is the catheter tip being completely surrounded by CSF. Infusion tests provide functional and reliable assessment of shunt patency in vivo and are strongly correlated with the position of the ventricular catheter on CT imaging.

Assessment of non-invasive ICP during CSF infusion test: an approach with transcranial Doppler.

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 < 0.05). nICP_FVd and nICP_CrCP presented non-significant correlations: -0.17 (p = 0.21), 0.21 (p = 0.13). For changes in ICP during individual infusion test nICP_PI, nICP_BB and nICP_FVd presented similar correlations with ICP: 0.39 ± 0.40, 0.39 ± 0.43 and 0.35 ± 0.41 respectively. However, nICP_CrCP presented a weaker correlation (R = 0.29 ± 0.24). CONCLUSIONS: Out of the four methods, nICP_PI was the one with best performance for predicting changes in ∆ICP during infusion test, followed by nICP_BB. Unreliable correlations were shown by nICP_FVd and nICP_CrCP. Changes of ICP observed during the test were expressed by nICP values with only moderate correlations.

Repeatability of cerebrospinal fluid constant rate infusion study.

OBJECTIVE: Infusion tests are important tools to assess cerebrospinal fluid (CSF)dynamics used in the preoperative selection of patients for shunt surgery, or to predict the scope of improvement from shunt revision. The aim of this study was to assess the repeatability of the key quantitative parameters describing CSF dynamics that are determined with infusion testing. MATERIALS AND METHODS: Eighteen patients in whom a constant infusion test was repeated within 102 days, without any intermediate surgical intervention, were studied. From each test baseline ICP, baseline pulse amplitude, outflow resistance, elastance coefficient and slope of the amplitude-pressure line were calculated and investigated with a regression and Bland-Altman analysis. RESULTS: Significant correlations (P < 0.01) were found for the outflow resistance (R = 0.96), the elastance coefficient (R = 0.778) and the slope of the amplitude-pressure line (R = 0.876). The estimated 95% confidence level for outflow resistance was 3 mmHg/ml min. Likewise, the elastance coefficient lay within a range of 0.16/ml and the slope of the amplitude-pressure line within 0.25. The most inconsistent parameter found were baseline ICP (R = 0.272) and baseline pulse amplitude (R = 0.171). CONCLUSION: The results of this study imply that the parameters resulting from an infusion study have to be considered within a range rather than as an absolute value.

What comes first? The dynamics of cerebral oxygenation and blood flow in response to changes in arterial pressure and intracranial pressure after head injury.

BACKGROUND: Brain tissue partial oxygen pressure (Pbt(O(2))) and near-infrared spectroscopy (NIRS) are novel methods to evaluate cerebral oxygenation. We studied the response patterns of Pbt(O(2)), NIRS, and cerebral blood flow velocity (CBFV) to changes in arterial pressure (AP) and intracranial pressure (ICP). METHODS: Digital recordings of multimodal brain monitoring from 42 head-injured patients were retrospectively analysed. Response latencies and patterns of Pbt(O(2)), NIRS-derived parameters [tissue oxygenation index (TOI) and total haemoglobin index (THI)], and CBFV reactions to fluctuations of AP and ICP were studied. RESULTS: One hundred and twenty-one events were identified. In reaction to alterations of AP, ICP reacted first [4.3 s; inter-quartile range (IQR) -4.9 to 22.0 s, followed by NIRS-derived parameters and CBFV (10.9 s; IQR: -5.9 to 39.6 s, 12.1 s; IQR: -3.0 to 49.1 s, 14.7 s; IQR: -8.8 to 52.3 s for THI, CBFV, and TOI, respectively), with Pbt(O(2)) reacting last (39.6 s; IQR: 16.4 to 66.0 s). The differences in reaction time between NIRS parameters and Pbt(O(2)) were significant (P<0.001). Similarly when reactions to ICP changes were analysed, NIRS parameters preceded Pbt(O(2)) (7.1 s; IQR: -8.8 to 195.0 s, 18.1 s; IQR: -20.6 to 80.7 s, 22.9 s; IQR: 11.0 to 53.0 s for THI, TOI, and Pbt(O(2)), respectively). Two main patterns of responses to AP changes were identified. With preserved cerebrovascular reactivity, TOI and Pbt(O(2)) followed the direction of AP. With impaired cerebrovascular reactivity, TOI and Pbt(O(2)) decreased while AP and ICP increased. In 77% of events, the direction of TOI changes was concordant with Pbt(O(2)). CONCLUSIONS: NIRS and transcranial Doppler signals reacted first to AP and ICP changes. The reaction of Pbt(O(2)) is delayed. The results imply that the analysed modalities monitor different stages of cerebral oxygenation.

Temozolomide responsiveness in aggressive corticotroph tumours: a case report and review of the literature.

Pituitary carcinoma occurs in ~0.2% of resected pituitary tumours and carries a poor prognosis (mean survival <4 years), with standard chemotherapy regimens showing limited efficacy. Recent evidence suggests that temozolomide (TMZ), an orally-active alkylating agent used principally in the management of glioblastoma, may also be effective in controlling aggressive/invasive pituitary adenomas/carcinomas. A low level of expression of the DNA-repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) predicts TMZ responsiveness in glioblastomas, and a similar correlation has been observed in the majority of aggressive pituitary adenomas/carcinomas reported to date. Here, we report a case of a silent pituitary corticotroph adenoma, which subsequently re-presented with Cushing's syndrome due to functioning hepatic metastases. The tumour exhibited low immunohistochemical MGMT expression in both primary (pituitary) and secondary (hepatic) lesions. Initial TMZ therapy (200 mg/m² for 5 days every 28 days-seven cycles) resulted in marked clinical, biochemical [>50% fall in adrenocorticotrophic hormone (ACTH)] and radiological [partial RECIST (response evaluation criteria in solid tumors) response] improvements. The patient then underwent bilateral adrenalectomy. However, despite reintroduction of TMZ therapy (further eight cycles) ACTH levels plateaued and no further radiological regression was observed. We review the existing literature reporting TMZ efficacy in pituitary corticotroph tumours, and highlight the pointers/lessons for treating aggressive pituitary neoplasia that can be drawn from experience of susceptibility and evolving resistance to TMZ therapy in glioblastoma. Possible strategies for mitigating resistance developing during TMZ treatment of pituitary adenomas/carcinomas are also considered.

Critical thresholds for cerebrovascular reactivity after traumatic brain injury.

INTRODUCTION: Pressure-reactivity index (PRx) is a useful tool in brain monitoring of trauma patients, but the question remains about its critical values. Using our TBI database, we identified the thresholds for PRx and other monitored parameters that maximize the statistical difference between death/survival and favorable/unfavorable outcomes. We also investigated how these thresholds depend on clinical factors such as age, gender and initial GCS. METHODS: A total of 459 patients from our database were eligible. Tables of 2 × 2 format were created grouping patients according to survival/death or favorable/unfavorable outcomes and varying thresholds for PRx, ICP and CPP. Pearson's chi square was calculated, and the thresholds returning the highest score were assumed to have the best discriminative value. The same procedure was repeated after division according to clinical factors. RESULTS: In all patients, we found that PRx had different thresholds for survival (0.25) and for favorable outcome (0.05). Thresholds of 70 mmHg for CPP and 22 mmHg for ICP were identified for both survival and favorable outcomes. The ICP threshold for favorable outcome was lower (18 mmHg) in females and patients older than 55 years. In logistic regression models, independent variables associating with mortality and unfavorable outcome were age, GCS, ICP and PRx. CONCLUSION: The prognostic role of PRx is confirmed but with a lower threshold of 0.05 for favorable outcome than for survival (0.25). Results for ICP are in line with current guidelines. However, the lower value in elderly and in females suggests increased vulnerability to intracranial hypertension in these groups.

Cerebral arterial compliance in patients with internal carotid artery disease.

BACKGROUND: A decrease in arterial compliance of the internal carotid artery has been associated with an increased risk in ipsilateral ischaemic stroke. However, so far, no technique has been validated to monitor the compliance of intracerebral arteries (Ca) in patients with carotid artery disease. In this study, we sought to monitor Ca in patients with unilateral symptomatic disease and to determine its variations during changes in PaCO(2). METHODS: We studied 18 patients with unilateral symptomatic internal carotid artery stenosis >50% or occlusion. Patients underwent monitoring of arterial blood pressure (ABP) and middle cerebral artery cerebral blood flow velocities (CBFV) during baseline, hyperventilation and 5%CO(2) inhalation. Ca was calculated from pulsatile amplitudes of ABP and Cerebral arterial blood volume, extracted from the CBFV waveform using a new mathematical model. RESULTS: At baseline, the decrease in Ca on the diseased side was correlated with the degree of stenosis (r = -0.35; P = 0.01). During hypocapnia, Ca was lower compared to baseline on the normal side (P = 0.004) and on the diseased side (P = 0.04). Ca reactivity, reflecting the changes in Ca per changes in 1 mmHg PaCO(2), was lower on the diseased side between baseline and hypocapnia (3.4 vs. 2.6%; P = 0.04). During hypercapnia, no changes in Ca on the diseased (P = 0.8) nor on the normal sides (P = 0.2) were observed. CONCLUSIONS: The decrease in cerebral arterial compliance the side of stenosis/occlusion was correlated with the severity of the internal carotid artery disease. Further studies are needed to determine whether Ca may improve the prediction of ischaemic events in symptomatic and asymptomatic patients.

Impact of duration of symptoms on CSF dynamics in idiopathic normal pressure hydrocephalus.

OBJECTIVE: Cerebrospinal fluid (CSF) pressure-volume compensation may change over time as part of normal ageing, where the resistance to CSF outflow increases and the formation of CSF decreases with age. Is CSF compensation dependent on duration of symptoms in idiopathic normal pressure hydrocephalus (iNPH)? METHODS: We investigated 92 patients presenting with iNPH. Mean age was 73 (range 47-86). There were 60 men and 32 women. They all presented with gait disturbance and ventricular dilatation. Memory deficit occurred in 72% and urinary incontinence in 52% of patients. All patients underwent computerized CSF infusion tests. Sixty-four shunted patients were available for follow-up, and their improvement was expressed using the NPH score. RESULTS: Mean intracranial pressure (ICP) was 10.1±5.1 mmHg, and mean resistance to CSF outflow was 17.3±5.2 mmHg/(ml/min). Mean duration of symptoms was 24±19 months (range from 2 weeks to 86 months). Baseline ICP, magnitude of ICP pulse waveform, brain compliance and improvement after shunting (72% of patients improved) did not exhibit any dependency on the duration of symptoms. The resistance to CSF outflow showed a strong tendency to decrease in time with the duration of symptoms beyond 2 years (R= -0.702; P<0.005). CONCLUSION: This is a preliminary observation, and it suggests that for patients with duration of symptoms longer than 2-3 years, the threshold for normal resistance to CSF outflow should be duration-adjusted.

Clinical assessment of cerebrospinal fluid dynamics in hydrocephalus. Guide to interpretation based on observational study.

OBJECTIVES: 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 often encountered in shunted patients to predict the scope for improvement by shunt re-adjustment or revision. In this study we aimed to update our knowledge of how key quantitative parameters describing CSF dynamics may be used in diagnosis of shunt-responsive hydrocephalus and in the assessment of shunt function. METHODS: A number of quantitative parameters [including resistance to CSF outflow (Rcsf), pulse amplitude of intracranial pressure waveform (AMP), RAP index and slow vasogenic waves] were studies in 1423 patients with 2665 CSF infusion tests and 305 overnight intracranial pressure (ICP)-monitoring sessions over a 17 year period. OBSERVATIONS: We demonstrate our observations for typical values of Pb, Rcsf, AMP, slow vasogenic waves derived from infusion studies or overnight ICP monitoring in differentiating atrophy from shunt-responsive normal pressure hydrocephalus or acute hydrocephalus. From the same variables tested on shunted patients we demonstrate a standardised approach to help differentiate a properly-functioning shunt from underdrainage or overdrainage. CONCLUSIONS: Quantitative variables derived from CSF dynamics allow differentiation between clinically overlapping entities such as shunt-responsive normal pressure hydrocephalus and brain atrophy (not shunt responsive) as well as allowing the detection of shunt malfunction (partial or complete blockage) or overdrainage. This observational study is intended to serve as an update for our understanding of quantitative testing of CSF dynamics.

Detecting residual cognitive function in disorders of consciousness.

Clinical audits have suggested up to 40% of patients with disorders of consciousness may be misdiagnosed, in part, due to the highly subjective process of determining, from a patient's behaviour, whether they retain awareness of self or environment. To address this problem, objective neuroimaging methods, such as positron emission tomography and functional magnetic resonance imaging have been explored. Using these techniques, paradigms, which do not require the patient to move or speak, can be used to determine a patient's level of residual cognitive function. Indeed, visual discrimination, speech comprehension and even the ability to respond to command have been demonstrated in some patients who are assumed to be vegetative on the basis of standard behavioural assessments. Functional neuroimaging is now increasingly considered to be a very useful and necessary addition to the clinical assessment process, where there is concern about the accuracy of the diagnosis and the possibility that residual cognitive function has remained undetected. In this essay, the latest neuroimaging findings are reviewed, the limitations and caveats pertaining to interpretation are outlined and the necessary developments, before neuroimaging becomes a standard component of the clinical assessment are discussed.

Pulsatile intracranial pressure and cerebral autoregulation after traumatic brain injury.

BACKGROUND: Strong correlation between mean intracranial pressure (ICP) and its pulse wave amplitude (AMP) has been demonstrated in different clinical scenarios. We investigated the relationship between invasive mean arterial blood pressure (ABP) and AMP to explore its potential role as a descriptor of cerebrovascular pressure reactivity after traumatic brain injury (TBI). METHODS: We retrospectively analyzed data of patients suffering from TBI with brain monitoring. Transcranial Doppler blood flow velocity, ABP, ICP were recorded digitally. Cerebral perfusion pressure (CPP) and AMP were derived. A new index-pressure-amplitude index (PAx)-was calculated as the Pearson correlation between (averaged over 10 s intervals) ABP and AMP with a 5 min long moving average window. The previously introduced transcranial Doppler-based autoregulation index Mx was evaluated in a similar way, as the moving correlation between blood flow velocity and CPP. The clinical outcome was assessed after 6 months using the Glasgow outcome score. RESULTS: 293 patients were studied. The mean PAx was -0.09 (standard deviation 0.21). This negative value indicates that, on average, an increase in ABP causes a decrease in AMP and vice versa. PAx correlated strong with Mx (R (2) = 0.46, P < 0.0002). PAx also correlated with age (R (2) = 0.18, P < 0.05). PAx was found to have as good predictive outcome value (area under curve 0.71, P < 0.001) as Mx (area under curve 0.69, P < 0.001). CONCLUSIONS: We demonstrated significant correlation between the known cerebral autoregulation index Mx and PAx. This new index of cerebrovascular pressure reactivity using ICP pulse wave information showed to have a strong association with outcome in TBI patients.

Towards the routine use of brain imaging to aid the clinical diagnosis of disorders of consciousness.

Clinical audits have highlighted the many challenges and dilemmas faced by clinicians assessing persons with disorders of consciousness (vegetative state and minimally conscious state). The diagnostic decision-making process is highly subjective, dependent upon the skills of the examiner and invariably dictated by the patients' ability to move or speak. Whilst a considerable amount has been learnt since Jennett and Plum coined the term 'vegetative state', the assessment process remains largely unchanged; conducted at the bedside, using behavioural assessment tools, which are susceptible to environmental and physiological factors. This has created a situation where the rate of misdiagnosis is unacceptably high (up to 43%). In order to address these problems, various functional brain imaging paradigms, which do not rely upon the patient's ability to move or speak, have been proposed as a source of additional information to inform the diagnostic decision making process. Although accumulated evidence from brain imaging, particularly functional magnetic resonance imaging (fMRI), has been encouraging, the empirical evidence is still based on relatively small numbers of patients. It remains unclear whether brain imaging is capable of informing the diagnosis beyond the behavioural assessment and whether brain imaging has any prognostic utility. In this study, we describe the functional brain imaging findings from a group of 41 patients with disorders of consciousness, who undertook a hierarchical speech processing task. We found, contrary to the clinical impression of a specialist team using behavioural assessment tools, that two patients referred to the study with a diagnosis of vegetative state did in fact demonstrate neural correlates of speech comprehension when assessed using functional brain imaging. These fMRI findings were found to have no association with the patient's behavioural presentation at the time of investigation and thus provided additional diagnostic information beyond the traditional clinical assessment. Notably, the utility of brain imaging was further underlined by the finding that the level of auditory processing revealed by functional brain imaging, correlated strongly (rs = 0.81, P < 0.001) with the patient's subsequent behavioural recovery, 6 months after the scan, suggesting that brain imaging may also provide valuable prognostic information. Although further evidence is required before consensus statements can be made regarding the use of brain imaging in clinical decision making for disorders of consciousness, the results from this study clearly highlight the potential of imaging to inform the diagnostic decision-making process for persons with disorders of consciousness.

In vivo assessment of hydrocephalus shunt.

OBJECTIVES: Over a 3-year period, we have performed 312 tests in 197 shunted patients. The data have been analyzed retrospectively to: (1) investigate the parameters describing CSF dynamics that correlate with shunt under-drainage and (2) estimate accuracy of this method. METHODS: Constant rate infusion tests into shunt prechamber were performed. RESULTS: In 161 of the 312 infusion tests, results indicated under-draining shunts. Patients in the under-draining group had higher baseline and plateau CSF pressures, higher resistance to CSF outflow and higher levels of baseline pulse amplitude waveform. During the test, a significantly greater vasogenic waves and lower compensatory reserve was noticed in patients with blocked shunts. In 21 patients with suggestion of shunt blockage and who subsequently underwent operative revision of the shunt, reports of intraoperative shunt patency were available. Shunt blockage was confirmed intra-operatively during surgery in 19 cases. CONCLUSIONS: In vivo shunt testing is easy, safe and clinically useful, aiding decision in difficult clinical situations, where shunt malfunction is suspected but not certain. It also has satisfactory positive predictive power.

Imaging regional variation of cellular proliferation in gliomas using 3'-deoxy-3'-[18F]fluorothymidine positron-emission tomography: an image-guided biopsy study.

AIM: To compare regional variations in uptake of 3'-deoxy-3'- [(18)F]-fluorothymidine (FLT) images using positron-emission tomography (PET) with measures of cellular proliferation from biopsy specimens obtained by image-guided brain biopsies. MATERIALS AND METHODS: Fourteen patients with a supratentorial glioma that required an image-guided brain biopsy were imaged preoperatively with dynamic PET after the administration of FLT. Maps of FLT irreversible uptake rate (K(i)) and standardized uptake value (SUV) were calculated. These maps were co-registered to a gadolinium-enhanced T1-weighted spoiled gradient echo (SPGR) sequence that was used for biopsy guidance, and the mean and maximum K(i) and SUV determined for each biopsy site. These values were correlated with the MIB-1 labelling index (a tissue marker of proliferation) from these biopsy sites. RESULTS: A total of 57 biopsy sites were studied. Although all measures correlated with MIB-1 labelling index, K(i)(max) provided the best correlation (Pearson coefficient, r=0.68; p<0.001). In low-grade gliomas the K(i)(mean) (+/-SD) was significantly higher than in normal tissue (3.3+/-1.7x10(-3)ml(plasma)/min/ml(tissue) versus 1.2+/-0.7x10(-3)ml(plasma)/min/ml(tissue); p=0.001). High-grade gliomas showed heterogeneous uptake with a mean K(i) of 7.7+/-4x10(-3)ml(plasma)/min/ml(tissue). A threshold K(i)(mean) of 1.8x10(-3) differentiates between normal tissue and tumour (sensitivity 84%, specificity 88%); however, the latter threshold underestimated the extent of tumour in half the cases. SUV closely agreed with K(i) measurements. CONCLUSION: FLT PET is a useful marker of cellular proliferation that correlates with regional variation in cellular proliferation; however, it is unable to identify the margin of gliomas.

Head injury rehabilitation: the role of a neurotrauma clinic.

Survivors of head injury are often left with varying degrees of disability and complex and varied needs, necessitating prolonged periods of rehabilitation and continuing care. Advances have been made in the acute management of these patients, but continuing management in terms of rehabilitation remains deficient with lack of specialist resources and a fragmented service. For head-injured patients, lack of access to appropriate ongoing rehabilitation may have profound effects on outcome and social re-integration. There are also considerable economic implications for planning and provision of services. The aims of this paper are to describe, review and evaluate the role of a Neurotrauma clinic within the Head Injury Service at Addenbrooke's Hospital, Cambridge. The multidisciplinary Neurotrauma clinic commenced in June 2003 following an extensive collaborative research programme to assess current regional head injury service provision and address deficiencies and management issues. Patients of all ages with ongoing problems following varying severity of head injury are followed up at 2 months + post-injury for as long as appropriate. Patients complete an SF-36 and GOSE questionnaire at each clinic appointment and this self-reported data is complemented by neuropsychological assessments, and demographic data entered on a database. The clinic acts as a 'gateway' to access appropriate ongoing rehabilitation and a source of information and support. The routine collection of outcome data enables tracking of individual patient progress and outcome and provides an information resource for further research. The findings highlight deficiencies in rehabilitation both in general service provision and specific patient need. Evidence in support of demand, need and effectiveness of rehabilitation for head injury is particularly relevant within the limited resources of the NHS. Early indications show that a specialist clinic can assist in providing continuity of patient care, in improving coordination of services, and act as a resource for further research on epidemiology, outcome and impact of rehabilitation.

Can electromyography objectively detect voluntary movement in disorders of consciousness?

Determining conscious processing in unresponsive patients relies on subjective behavioural assessment. Using data from hand electromyography, the authors studied the occurrence of subthreshold muscle activity in response to verbal command, as an objective indicator of awareness in 10 disorders of consciousness patients. One out of eight vegetative state patients and both minimally conscious patients (n = 2) demonstrated an increased electromyography signal specifically linked to command. These findings suggest electromyography could be used to assess awareness objectively in pathologies of consciousness.

How does CSF dynamics change after shunting?

OBJECTIVE: Hydrocephalus is much more complex than a simple disorder of cerebrospinal fluid (CSF) circulation. Shunting primarily corrects disturbed fluid flow which may have an impact on cerebral blood flow and metabolism. We studied hydrocephalic patients before and after shunting to characterize changes in their CSF compensatory parameters. MATERIAL AND METHODS: We selected 25 patients and studied them retrospectively. All patients had ventriculomegaly and clinical symptoms of normal pressure hydrocephalus. After shunting, they were still presenting with some adverse symptoms, mainly headaches, slow improvement or no improvement of ventriculomegaly. Therefore, they underwent further infusion studies to assess shunt function. In all cases, the shunts were confirmed to be draining CSF adequately. Parameters of CSF dynamics: baseline intracranial pressure (ICP), resistance to CSF outflow, cerebrospinal elasticity, content of vasogenic pressure waves (pulse, respiratory and B waves) and compensatory reserve assessed as moving correlation coefficient between mean CSF pressure and pulse amplitude (RAP), were compared before and after shunting. RESULTS: Mean ICP and resistance to CSF outflow decreased (P < 0.003) after shunting. All vasogenic pressure waves decreased (P < 0.005). Compensatory reserve (RAP) significantly improved (P < 0.005). CONCLUSION: A functioning shunt has an important impact on CSF circulation and pressure-volume compensation. Infusion studies can demonstrate the return of disturbed CSF dynamics to normal values even if clinical or radiological changes are not dramatic.

Coupling of sagittal sinus pressure and cerebrospinal fluid pressure in idiopathic intracranial hypertension--a preliminary report.

BACKGROUND: Narrowing of the cranial dural venous sinuses has been implicated as contributing to elevated intracranial pressure in idiopathic intracranial hypertension [IIH]. Such narrowing may be either a fixed stenosis or secondary to raised ICP. We have investigated whether narrowing of the venous sinuses may reflect direct coupling between cerebrospinal fluid pressure and sagittal sinus pressure. METHODS: Nine patients with the clinical features of IIH [8F, 1M; mean age 41 (range 22-55)] were studied as part of their standard clinical investigations by simultaneous lumbar CSF infusion study and direct retrograde cerebral venography whereby a catheter is placed within the sagittal sinus under fluoroscopic guidance. FINDINGS: In all cases, both CSF pressure (Pcsf) and sagittal sinus pressure (Pss) were elevated with Pcsf slightly exceeding Pss (27.0 +/- 2.3 mm Hg. 25.2 +/- 7.5 mm Hg; difference P = 0.026; correlation R = 0.97, P = 0.0032). There was a gradient of pressure along the sagittal and transverse sinuses. CSF infusion provoked rises in both Pcsf and Pss (R = 0.97, P < 0.0007). During drainage of CSF after the test (8 cases), Pcsf decreased to values lower than Pss (-3.26 +/- 3.9 mm Hg; P = 0.0097). There was excellent correlation between slow waves of Pcsf and Pss (mean R = 0.9) and between baseline pulse amplitudes of both pressures (R = 0.91; P = 0.03). CONCLUSIONS: In the 9 patients studied with IIH, Pcsf and Pss were coupled both statically (mean values) and dynamically (vasogenic components). During drainage, both pressures decreased until probably central venous pressure was reached and then Pcsf decreased further while Pss remained constant. This suggests that, in many cases of IIH, there is functional obstruction of venous outflow through the dural sinuses. Raised Pcsf partly obstructs venous sinus outflow, thereby increasing Pss which, in turn, leads to a further rise in Pcsf, et sequor. This vicious cycle can be interrupted by draining CSF.

ICM+, a flexible platform for investigations of cerebrospinal dynamics in clinical practice.

BACKGROUND: ICM+ software encapsulates 20 years of our experience in brain monitoring gained in multiple neurosurgical and intensive care centres. It collects data from a variety of bedside monitors and produces on-line time trends of parameters defined using configurable signal processing formulas. The resulting data can be displayed in a variety of ways including time trends, histograms, cross histograms, correlations, etc. For technically minded researchers there is a plug-in mechanism facilitating registration of third party libraries of functions and analysis tools. METHODS: The latest version of the ICM+ software has been used in 162 severely head injured patients in the Neurosciences Critical Care Unit of the Addenbrooke's Cambridge University Hospital. Intracranial pressure (ICP) and invasive arterial blood pressure (ABP) were monitored routinely. Mean values of ICP, ABP, cerebral perfusion pressure (CPP) and various indices describing pressure reactivity (PRx), pressure-volume compensation (RAP) and vascular waveforms of ICP were calculated. Error-bar chart showing reactivity index PRx versus CPP ('Optimal CPP' chart) was calculated continuously. FINDINGS: PRx showed a significant relationship with CPP (ANOVA: p < 0.021) indicating loss of cerebral pressure-reactivity for low CPP (CPP < 55 mmHg) and for high CPPs (CPP > 95 mmHg). Examining PRx-CPP curves in individual patients revealed that CPP(OPT) not only varied between subjects but tended to fluctuate as the patient's state changed during the stay in the ICU. Calculation window of 6-8 h provided enough data to capture the CPP(OPT) curve. CONCLUSIONS: ICM+ software proved to be useful both academically and clinically. The complexity of data analysis is hidden inside loadable profiles thus allowing clinically minded investigators to take full advantage of signal processing engine in their research into cerebral blood and fluid dynamics.

Pulse amplitude of intracranial pressure waveform in hydrocephalus.

BACKGROUND: There is increasing interest in evaluation of the pulse amplitude of intracranial pressure (AMP) in explaining dynamic aspects of hydrocephalus. We reviewed a large number of ICP recordings in a group of hydrocephalic patients to assess utility of AMP. MATERIALS AND METHODS: From a database including approximately 2,100 cases of infusion studies (either lumbar or intraventricular) and overnight ICP monitoring in patients suffering from hydrocephalus of various types (both communicating and non-communicating), etiology and stage of management (non-shunted or shunted) pressure recordings were evaluated. For subgroup analysis we selected 60 patients with idiopathic NPH with full follow-up after shunting. In 29 patients we compared pulse amplitude during an infusion study performed before and after shunting with a properly functioning shunt. Amplitude was calculated from ICP waveforms using spectral analysis methodology. FINDINGS: A large amplitude was associated with good outcome after shunting (positive predictive value of clinical improvement for AMP above 2.5 mmHg was 95%). However, low amplitude did not predict poor outcome (for AMP below 2.5 mmHg 52% of patients improved). Correlations of AMP with ICP and Rcsf were positive and statistically significant (N = 131 with idiopathic NPH; R = 0.21 for correlation with mean ICP and 0.22 with Rcsf; p< 0.01). Correlation with the brain elastance coefficient (or PVI) was not significant. There was also no significant correlation between pulse amplitude and width of the ventricles. The pulse amplitude decreased (p < 0.005) after shunting. CONCLUSIONS: Interpretation of the ICP pulse waveform may be clinically useful in patients suffering from hydrocephalus. Elevated amplitude seems to be a positive predictor for clinical improvement after shunting. A properly functioning shunt reduces the pulse amplitude.