Prevalence of pineal cysts in healthy individuals: Emphasis on size, morphology and pineal recess crowding.

The present study aimed to determine prevalence of non-hydrocephalic pineal cysts of different size and morphology in healthy individuals. In a cohort of healthy individuals who as part of research volunteered to undergo magnetic resonance imaging (MRI) of the brain, we performed a systematic search for occurrence of pineal cysts of different sizes, morphology and evidence of crowding of the pineal recess. Degree of crowding in the pineal recess was estimated by the imaging biomarkers anterior-posterior diameter and cyst-tectum-splenium (CTS) ratio at midsagittal MRI. The study included a cohort of 994 healthy individuals, aged 47.0 ± 21.1 years in whom a pineal cyst was demonstrated in 337/994 (37.5%) individuals. A small cyst within a mainly solid gland was observed in 252/994 (25.4%) subjects and a mainly cystic gland in121/994 (12.2%). The pineal cysts were more frequent in women than men, and were associated with age, though not with reduced prevalence in aged individuals, as previously reported. Cysts with maximum anterior-posterior diameter ≥ 10 mm were seen in 51/994 (5.1%) individuals, and with CTS ratio ≥ 0.9 in 16/994 (1.6%) individuals. The occurrence of pineal cysts is frequent and is seen more frequently in women. It usually presents as a small cyst in a predominantly solid gland; however, pineal cysts causing crowding of the pineal recess with a CTS ratio ≥ 0.9 was seen in merely 1.6% of participants.

Radiological predictors of shunt response in the diagnosis and treatment of idiopathic normal pressure hydrocephalus: a systematic review and meta-analysis.

BACKGROUND: Patients with the dementia subtype idiopathic normal pressure hydrocephalus (iNPH) may improve clinically following cerebrospinal fluid (CSF) diversion (shunt) surgery, though the predictors of shunt response remain debated. Currently, radiological features play an important role in the diagnosis of iNPH, but it is not well established which radiological markers most precisely predict shunt responsive iNPH. OBJECTIVE: To conduct a systematic review and meta-analysis to identify radiological predictors of shunt responsiveness, evaluate their diagnostic effectiveness, and recommend the most predictive radiological features. METHODS: Embase, MEDLINE, Scopus, PubMed, Google Scholar, and JSTOR were searched for original studies investigating radiological predictors of shunt response in iNPH patients. Included studies were assessed using the ROBINS-1 tool, and eligible studies were evaluated using a univariate meta-analysis. RESULTS: Overall, 301 full-text papers were screened, of which 28 studies were included, and 26 different radiological features were identified, 5 of these met the inclusion criteria for the meta-analysis: disproportionately enlarged subarachnoid space (DESH), callosal angle, periventricular white matter changes, cerebral blood flow (CBF), and computerized tomography cisternography. The meta-analysis showed that only callosal angle and periventricular white matter changes significantly differentiated iNPH shunt responders from non-responders, though both markers had a low diagnostic odds ratio (DOR) of 1.88 and 1.01 respectively. None of the other radiological markers differentiated shunt responsive from shunt non-responsive iNPH. CONCLUSION: Callosal angle and periventricular changes are the only diagnostically effective radiological predictors of shunt responsive iNPH patients. However, due to the DORs approximating 1, they are insufficient as sole predictors and are advised to be used only in combination with other diagnostic tests of shunt response. Future research must evaluate the combined use of multiple radiological predictors, as it may yield beneficial additive effects that may allow for more robust radiological shunt response prediction.

Early surgical versus endovascular repair of ruptured blood-blister aneurysm of the internal carotid artery: a single-center 20-year experience.

OBJECTIVE: Early repair of ruptured blood-blister aneurysms (BBAs) of the internal carotid artery (ICA) remains challenging. Although both surgical and endovascular therapies have been established, their relative superiority remains debated. The authors assessed their single-center experience and compared early deconstructive versus reconstructive repair and early reconstructive surgical versus endovascular repair of ruptured BBAs of the ICA. METHODS: The study included patients who underwent repair of ruptured BBAs of the ICA within 1 week after the ictus during a 20-year period. Multiple variables were recorded, including clinical state, severity of subarachnoid hemorrhage (SAH), characteristics of the BBA, treatment details, complication profile, need for secondary treatment, and clinical outcome. RESULTS: In total, 27 patients underwent early surgical (n = 16) or endovascular (n = 11) repair of BBAs at a median of 24 hours (range 9-120 hours) after the ictus during the period from September 2000 to June 2021 (20.4 years). Primary deconstructive repair (n = 6) without bypass was accompanied by middle cerebral artery (MCA) territory infarction in 5 of 6 (83%) patients and a high mortality rate (4/6 [67%]). Among the 21 patients who underwent early reconstructive repair, surgery was performed in 11 patients (clipping in 6 and clip-wrapping in 5 patients) and endovascular repair in 10 patients (flow diversion in 7 and stent/stent-assisted coiling in 3 patients). No differences were found in complication profiles or clinical outcomes between the surgical and endovascular groups. The mortality rate was low (2/21 [9.5%]), with 1 fatality in each group. CONCLUSIONS: From the authors' experience, both surgical and endovascular approaches permitted reconstructive repair of ruptured BBAs of the ICA, with no modality proving superior. Reconstructive treatment is preferable to ICA sacrifice, and if sacrifice is chosen, it should be accompanied with bypass surgery or delayed to the phase when cerebral vasospasm has resumed. The rare occurrence of this disease calls for prospective multicenter studies to improve treatment and delineate which modality is preferable in individual cases.

Cerebrospinal fluid and venous biomarkers of shunt-responsive idiopathic normal pressure hydrocephalus: a systematic review and meta-analysis.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease and dementia subtype involving disturbed cerebrospinal fluid (CSF) homeostasis. Patients with iNPH may improve clinically following CSF diversion through shunt surgery, but it remains a challenge to predict which patients respond to shunting. It has been proposed that CSF and blood biomarkers may be used to predict shunt response in iNPH. OBJECTIVE: To conduct a systematic review and meta-analysis to identify which CSF and venous biomarkers predict shunt-responsive iNPH most accurately. METHODS: Original studies that investigate the use of CSF and venous biomarkers to predict shunt response were searched using the following databases: Embase, MEDLINE, Scopus, PubMed, Google Scholar, and JSTOR. Included studies were assessed using the ROBINS-I tool, and eligible studies were evaluated utilising univariate meta-analyses. RESULTS: The study included 13 studies; seven addressed lumbar CSF levels of amyloid-ß 1-42, nine studies CSF levels of Total-Tau, six studies CSF levels of Phosphorylated-Tau, and seven studies miscellaneous biomarkers, proteomics, and genotyping. A meta-analysis of six eligible studies conducted for amyloid-ß 1-42, Total-Tau, and Phosphorylated-Tau demonstrated significantly increased lumbar CSF Phosphorylated-Tau (- 0.55 SMD, p = 0.04) and Total-Tau (- 0.50 SMD, p = 0.02) in shunt-non-responsive iNPH, though no differences were seen between shunt responders and non-responders for amyloid-ß 1-42 (- 0.26 SMD, p = 0.55) or the other included biomarkers. CONCLUSION: This meta-analysis found that lumbar CSF levels of Phosphorylated-Tau and Total-Tau are significantly increased in shunt non-responsive iNPH compared to shunt-responsive iNPH. The other biomarkers, including amyloid-ß 1-42, did not significantly differentiate shunt-responsive from shunt-non-responsive iNPH. More studies on the Tau proteins examining sensitivity and specificity at different cut-off levels are needed for a robust analysis of the diagnostic efficiency of the Tau proteins.

Clinical application of intrathecal gadobutrol for assessment of cerebrospinal fluid tracer clearance to blood.

BACKGROUNDMethodology for estimation of cerebrospinal fluid (CSF) tracer clearance could have wide clinical application in predicting excretion of intrathecal drugs and metabolic solutes from brain metabolism and for diagnostic workup of CSF disturbances.METHODSThe MRI contrast agent gadobutrol (Gadovist) was used as a CSF tracer and injected into the lumbar CSF. Gadobutrol is contained outside blood vessels of the CNS and is eliminated along extravascular pathways, analogous to many CNS metabolites and intrathecal drugs. Tracer enrichment was verified and assessed in CSF by MRI at the level of the cisterna magna in parallel with obtaining blood samples through 48 hours.RESULTSIn a reference patient cohort (n = 29), both enrichment within CSF and blood coincided in time. Blood concentration profiles of gadobutrol through 48 hours varied between patients diagnosed with CSF leakage (n = 4), idiopathic normal pressure hydrocephalus dementia (n = 7), pineal cysts (n = 8), and idiopathic intracranial hypertension (n = 4).CONCLUSIONAssessment of CSF tracer clearance is clinically feasible and may provide a way to predict extravascular clearance of intrathecal drugs and endogenous metabolites from the CNS. The peak concentration in blood (at about 10 hours) was preceded by far peak tracer enhancement at MRI in extracranial lymphatic structures (at about 24 hours), as shown in previous studies, indicating a major role of the spinal canal in CSF clearance capacity.FUNDINGThe work was supported by the Department of Neurosurgery, Oslo University Hospital; the Norwegian Institute for Air Research; and the University of Oslo.

Clearance of interstitial fluid (ISF) and CSF (CLIC) group-part of Vascular Professional Interest Area (PIA): Cerebrovascular disease and the failure of elimination of Amyloid-ß from the brain and retina with age and Alzheimer's disease-Opportunities for Therapy.

Two of the key functions of arteries in the brain are (1) the well-recognized supply of blood via the vascular lumen and (2) the emerging role for the arterial walls as routes for the elimination of interstitial fluid (ISF) and soluble metabolites, such as amyloid beta (Aß), from the brain and retina. As the brain and retina possess no conventional lymphatic vessels, fluid drainage toward peripheral lymph nodes is mediated via transport along basement membranes in the walls of capillaries and arteries that form the intramural peri-arterial drainage (IPAD) system. IPAD tends to fail as arteries age but the mechanisms underlying the failure are unclear. In some people this is reflected in the accumulation of Aß plaques in the brain in Alzheimer's disease (AD) and deposition of Aß within artery walls as cerebral amyloid angiopathy (CAA). Knowledge of the dynamics of IPAD and why it fails with age is essential for establishing diagnostic tests for the early stages of the disease and for devising therapies that promote the clearance of Aß in the prevention and treatment of AD and CAA. This editorial is intended to introduce the rationale that has led to the establishment of the Clearance of Interstitial Fluid (ISF) and CSF (CLIC) group, within the Vascular Professional Interest Area of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment.

In Vivo Imaging of Molecular Clearance From Human Entorhinal Cortex: A Possible Method for Preclinical Testing of Dementia.

Accumulation in the brain of metabolic waste products such as amyloid-ß and hyperphosporylated tau (tau) is a hallmark of dementia (e.g., Alzheimer's disease). One possible underlying mechanism is impaired cerebral paravascular (glymphatic) clearance of toxic solutes. Recently, we have provided evidence of glymphatic circulation being present in the human brain, utilizing repeated magnetic resonance imaging (MRI) acquisitions before/after intrathecal injection of an MRI contrast agent, serving as a cerebrospinal fluid (CSF) tracer (glymphatic MRI [gMRI]). In a recent study, we utilized the same methodology to assess glymphatic clearance function within an anatomical region that has a key role in cognitive function-the entorhinal cortex (ERC). gMRI was compared in individuals with the dementia subtype idiopathic normal pressure hydrocephalus (iNPH; n = 30) and reference (REF; n = 8) subjects. We found delayed clearance of CSF tracer from CSF nearby ERC, the ERC itself, and the white matter adjacent to ERC, which was most evident after 24 hr. The observations were interpreted as indicative of impaired glymphatic circulation and further suggested this being a possible mechanism behind accumulation of amyloid-ß and tau in ERC and instrumental for dementia in iNPH. We suggest that gMRI may serve as a tool for assessment of early dementia, or even in the preclinical stage.

Delayed clearance of cerebrospinal fluid tracer from entorhinal cortex in idiopathic normal pressure hydrocephalus: A glymphatic magnetic resonance imaging study.

The glymphatic system plays a key role for clearance of waste solutes from the rodent brain. We recently found evidence of glymphatic circulation in the human brain when using magnetic resonance imaging (MRI) contrast agent as cerebrospinal fluid (CSF) tracer in conjunction with multiple MRI acquisitions (gMRI). The present study explored the hypothesis that reduced glymphatic clearance in entorhinal cortex (ERC) may be instrumental in idiopathic normal pressure hydrocephalus (iNPH) dementia. gMRI acquisitions were obtained over a 24-48 h time span in cognitively affected iNPH patients and non-cognitively affected patients with suspected CSF leaks. The CSF tracer enrichment was determined as changes in normalized MRI T1 signal units. The study included 30 patients with iNPH and 8 individuals with suspected CSF leaks (i.e. reference individuals). Compared to reference individuals, iNPH patients presented with higher medial temporal lobe atrophy score and Evan's index and inferior ERC thickness. We found delayed clearance of the intrathecal CSF tracer gadobutrol from CSF, the ERC and adjacent white matter, suggesting impaired glymphatic circulation. Reduced clearance and accumulation of toxic waste product such as amyloid-ß may be a mechanism behind dementia in iNPH. Glymphatic MRI (gMRI) may become a tool for assessment of early dementia.

Brain-wide glymphatic enhancement and clearance in humans assessed with MRI.

To what extent does the subarachnoid cerebrospinal fluid (CSF) compartment communicate directly with the extravascular compartment of human brain tissue? Interconnection between the subarachnoid CSF compartment and brain perivascular spaces is reported in some animal studies, but with controversy, and in vivo CSF tracer studies in humans are lacking. In the present work, we examined the distribution of a CSF tracer in the human brain by MRI over a prolonged time span. For this, we included a reference cohort, representing close to healthy individuals, and a cohort of patients with dementia and anticipated compromise of CSF circulation (idiopathic normal pressure hydrocephalus). The MRI contrast agent gadobutrol, which is confined to the extravascular brain compartment by the intact blood-brain barrier, was used as a CSF tracer. Standardized T1-weighted MRI scans were performed before and after intrathecal gadobutrol at defined time points, including at 24 hours, 48 hours, and 4 weeks. All MRI scans were aligned and brain regions were segmented using FreeSurfer, and changes in normalized T1 signals over time were quantified as percentage change from baseline. The study provides in vivo evidence of access to all human brain subregions of a substance administered intrathecally. Clearance of the tracer substance was delayed in the dementia cohort. These observations translate previous findings in animal studies into humans and open new prospects concerning intrathecal treatment regimens, extravascular contrast-enhanced MRI, and assessment of brain clearance function.

Brain Capillary Ultrastructure in Idiopathic Normal Pressure Hydrocephalus: Relationship With Static and Pulsatile Intracranial Pressure.

Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease of unknown cause. We investigated the morphology of capillaries in frontal cortex biopsies from iNPH patients and related the observations to overnight intracranial pressure (ICP) scores. A biopsy (0.9×10 mm) was taken from where the ICP sensor subsequently was inserted. Brain capillaries were investigated by electron microscopy of biopsies from 27 iNPH patients and 10 reference subjects, i.e. patients (not healthy individuals) without cerebrospinal fluid circulation disturbances, in whom normal brain tissue was removed as part of necessary neurosurgical treatment. Degenerating and degenerated pericyte processes were identified in 23/27 (85%) iNPH and 6/10 (60%) of reference specimens. Extensive disintegration of pericyte processes were recognized in 11/27 (41%) iNPH and 1/10 (10%) reference specimens. There were no differences in basement membrane (BM) thickness or pericyte coverage between iNPH and reference subjects. The pulsatile or static ICP scores did neither correlate with the BM thickness nor with pericyte coverage. We found increased prevalence of degenerating pericytes in iNPH while the BM thickness and pericyte coverage did not differ from the reference individuals. Observations in iNPH may to some extent be age-related since the iNPH patients were significantly older than the reference individuals.

Intracranial Pressure Waveforms are More Closely Related to Central Aortic than Radial Pressure Waveforms: Implications for Pathophysiology and Therapy.

In patients with subarachnoid haemorrhage, pulsatile intracranial pressure (ICP) is more strongly associated with adverse events than mean ICP. Furthermore, patients with idiopathic normal-pressure hydrocephalus (iNPH), and pulsatile ICP of 5 mmHg or more, gain more benefit from cerebrospinal fluid (CSF) shunting than those whose pulsatile ICP is lower than 5 mmHg.Our study aims to investigate the morphological relationship between ICP pulsations, aortic pressure pulsations and radial artery pulsations. Central aortic pulse pressure has been known to be the best predictor of adverse cardiac events, whereas radial artery pulse pressure is generally measured and displayed in intensive care environments.We studied 10 patients with iNPH, and their ICP and aortic and radial pressures were digitised, ensemble-averaged and compared in the time and frequency domains. The ICP wave contour was quite different to the radial pressure waveform. By contrast, the ICP waveform was similar to the aortic pressure wave contour. The ICP amplitude averaged <10 % of aortic pulse pressure. In the frequency domain, the relative amplitude of the first three harmonics was similar for the ICP and aortic pressure. Hence, monitoring central aortic pressure through derivation from the radial pressure wave is superior to measurement of radial pressure alone.

The baseline pressure of intracranial pressure (ICP) sensors can be altered by electrostatic discharges.

BACKGROUND: The monitoring of intracranial pressure (ICP) has a crucial role in the surveillance of patients with brain injury. During long-term monitoring of ICP, we have seen spontaneous shifts in baseline pressure (ICP sensor zero point), which are of technical and not physiological origin. The aim of the present study was to explore whether or not baseline pressures of ICP sensors can be affected by electrostatics discharges (ESD's), when ESD's are delivered at clinically relevant magnitudes. METHODS: We performed bench-testing of a set of commercial ICP sensors. In our experimental setup, the ICP sensor was placed in a container with 0.9% NaCl solution. A test person was charged 0.5-10 kV, and then delivered ESD's to the sensor by touching a metal rod that was located in the container. The continuous pressure signals were recorded continuously before/after the ESD's, and the pressure readings were stored digitally using a computerized system RESULTS: A total of 57 sensors were tested, including 25 Codman ICP sensors and 32 Raumedic sensors. When charging the test person in the range 0.5-10 kV, typically ESD's in the range 0.5-5 kV peak pulse were delivered to the ICP sensor. Alterations in baseline pressure ≥ 2 mmHg was seen in 24 of 25 (96%) Codman sensors and in 17 of 32 (53%) Raumedic sensors. Lasting changes in baseline pressure > 10 mmHg that in the clinical setting would affect patient management, were seen frequently for both sensor types. The changes in baseline pressure were either characterized by sudden shifts or gradual drifts in baseline pressure. CONCLUSIONS: The baseline pressures of commercial solid ICP sensors can be altered by ESD's at discharge magnitudes that are clinically relevant. Shifts in baseline pressure change the ICP levels visualised to the physician on the monitor screen, and thereby reveal wrong ICP values, which likely represent a severe risk to the patient.

Cardiac output in idiopathic normal pressure hydrocephalus: association with arterial blood pressure and intracranial pressure wave amplitudes and outcome of shunt surgery.

BACKGROUND: In patients with idiopathic normal pressure hydrocephalus (iNPH) responding to shunt surgery, we have consistently found elevated intracranial pressure (ICP) wave amplitudes during diagnostic ICP monitoring prior to surgery. It remains unknown why ICP wave amplitudes are increased in these patients. Since iNPH is accompanied by a high incidence of vascular co-morbidity, a possible explanation is that there is reduced vascular compliance accompanied by elevated arterial blood pressure (ABP) wave amplitudes and even altered cardiac output (CO). To investigate this possibility, the present study was undertaken to continuously monitor CO to determine if it is correlated to ABP and ICP wave amplitudes and the outcome of shunting in iNPH patients. It was specifically addressed whether the increased ICP wave amplitudes seen in iNPH shunt responders were accompanied by elevated CO and/or ABP wave amplitude levels. METHODS: Prospective iNPH patients (29) were clinically graded using an NPH grading scale. Continuous overnight minimally-invasive monitoring of CO and ABP was done simultaneously with ICP monitoring; the CO, ABP, and ICP parameters were parsed into 6-second time windows. Patients were assessed for shunt surgery on clinical grade, Evan's index, and ICP wave amplitude. Follow-up clinical grading was performed 12 months after surgery. RESULTS: ICP wave amplitudes but not CO or ABP wave amplitude, showed good correlation with the response to shunt treatment. The patients with high ICP wave amplitude did not have accompanying high levels of CO or ABP wave amplitude. Correlation analysis between CO and ICP wave amplitudes in individual patients showed different profiles [significantly positive in 10 (35%) and significantly negative in 16 (55%) of 29 recordings]. This depended on whether there was also a correlation between ABP and ICP wave amplitudes and on the average level of ICP wave amplitude. CONCLUSIONS: These results gave no evidence that the increased levels of ICP wave amplitudes seen in iNPH shunt responders prior to surgery were accompanied by elevated levels of ABP wave amplitudes or elevated CO. In the individual patients the correlation between CO and ICP wave amplitude was partly related to an association between ABP and ICP wave amplitudes which can be indicative of the state of cerebrovascular pressure regulation, and partly related to the ICP wave amplitude which can be indicative of the intracranial compliance.

The pulsating brain: A review of experimental and clinical studies of intracranial pulsatility.

The maintenance of adequate blood flow to the brain is critical for normal brain function; cerebral blood flow, its regulation and the effect of alteration in this flow with disease have been studied extensively and are very well understood. This flow is not steady, however; the systolic increase in blood pressure over the cardiac cycle causes regular variations in blood flow into and throughout the brain that are synchronous with the heart beat. Because the brain is contained within the fixed skull, these pulsations in flow and pressure are in turn transferred into brain tissue and all of the fluids contained therein including cerebrospinal fluid. While intracranial pulsatility has not been a primary focus of the clinical community, considerable data have accrued over the last sixty years and new applications are emerging to this day. Investigators have found it a useful marker in certain diseases, particularly in hydrocephalus and traumatic brain injury where large changes in intracranial pressure and in the biomechanical properties of the brain can lead to significant changes in pressure and flow pulsatility. In this work, we review the history of intracranial pulsatility beginning with its discovery and early characterization, consider the specific technologies such as transcranial Doppler and phase contrast MRI used to assess various aspects of brain pulsations, and examine the experimental and clinical studies which have used pulsatility to better understand brain function in health and with disease.

Cerebrospinal fluid pulse pressure amplitude during lumbar infusion in idiopathic normal pressure hydrocephalus can predict response to shunting.

BACKGROUND: We have previously seen that idiopathic normal pressure hydrocephalus (iNPH) patients having elevated intracranial pressure (ICP) pulse amplitude consistently respond to shunt surgery. In this study we explored how the cerebrospinal fluid pressure (CSFP) pulse amplitude determined during lumbar infusion testing, correlates with ICP pulse amplitude determined during over-night ICP monitoring and with response to shunt surgery. Our goal was to establish a more reliable screening procedure for selecting iNPH patients for shunt surgery using lumbar intrathecal infusion. METHODS: The study population consisted of all iNPH patients undergoing both diagnostic lumbar infusion testing and continuous over-night ICP monitoring during the period 2002-2007. The severity of iNPH was assessed using our NPH grading scale before surgery and 12 months after shunting. The CSFP pulse was characterized from the amplitude of single pressure waves. RESULTS: Totally 62 iNPH patients were included, 45 of them underwent shunt surgery, in whom 78% were shunt responders. Among the 45 shunted patients, resistance to CSF outflow (R(out)) was elevated (>or= 12 mmHg/ml/min) in 44. The ICP pulse amplitude recorded over-night was elevated (i.e. mean ICP wave amplitude >or= 4 mmHg) in 68% of patients; 92% of these were shunt responders. In those with elevated overnight ICP pulse amplitude, we found also elevated CSFP pulse amplitude recorded during lumbar infusion testing, both during the opening phase following lumbar puncture and during a standardized period of lumbar infusion (15 ml Ringer over 10 min). The clinical response to shunting after 1 year strongly associated with the over-night ICP pulse amplitude, and also with the pulsatile CSFP during the period of lumbar infusion. Elevated CSFP pulse amplitude during lumbar infusion thus predicted shunt response with sensitivity of 88 and specificity of 60 (positive and negative predictive values of 89 and 60, respectively). CONCLUSIONS: In iNPH patients, shunt response can be anticipated in 9/10 patients with elevated overnight ICP pulse amplitude, while in only 1/10 with low ICP pulse amplitude. Additionally, the CSFP pulse amplitude during lumbar infusion testing was elevated in patients with elevated over-night ICP pulse amplitude. In particular, measurement of CSFP pulse amplitude during a standardized infusion of 15 ml Ringer over 10 min was useful in predicting response to shunt surgery and can be used as a screening procedure for selection of iNPH patients for shunting.

A dynamic nonlinear relationship between the static and pulsatile components of intracranial pressure in patients with subarachnoid hemorrhage.

OBJECT: In the search for optimal monitoring and predictive tools in neurocritical care, the relationship of the pulsatile component of intracranial pressure (ICP) and the pressure itself has long been of great interest. Higher pressure often correlates with a higher pulsatile response to the heartbeat, interpreted as a type of compliance curve. Various mathematical approaches have been used, but regardless of the formula used, it is implicitly assumed that a reproducible curve exists. The authors investigated the stability of the correlation between static and pulsatile ICPs in patients with subarachnoid hemorrhage (SAH) who were observed for several hours by using data sets large enough to allow such calculations to be made. METHODS: The ICP recordings were obtained in 39 patients with SAH and were parsed into 6-second time windows (1,998,944 windows in 197 recordings). The ICP parameters were computed for each window as follows: static ICP was defined as the mean ICP, and pulsatile ICP was characterized by mean ICP wave amplitude, rise time, and rise time coefficient. RESULTS: The mean ICP and ICP wave amplitudes were simultaneously high or low (the expected correlation) in only approximately 60% of observations. Furthermore, static and pulsatile ICP correlated well only over short intervals; the degree of correlation weakened over periods of hours and was inconsistent across patients and within individual patients over time. Decorrelation originated with abrupt shifting and gradual drifting of mean ICP and ICP wave amplitude over several hours. CONCLUSIONS: The relationship between the static and pulsatile components of ICPs changes over time. It evolves, even in individual patients, over a number of hours. This can be one reason the observation of high pulsatile ICP (indicative of reduced intracranial compliance) despite normal mean ICP that is seen in some patients with SAH. The meaning and potential clinical usefulness of such changes in the curves is uncertain, but it implies that clinical events result not only from moving further out on a compliance curve; in practice, the curve, and the biological system that underlies the curve, may itself change.

Cerebral microdialysis and intracranial pressure monitoring in patients with idiopathic normal-pressure hydrocephalus: association with clinical response to extended lumbar drainage and shunt surgery.

OBJECT: This study was performed in patients with idiopathic normal-pressure hydrocephalus (iNPH) to monitor cerebral metabolism with microdialysis (MD) and intracranial pressure (ICP) readings, and relate to the clinical responses to extended lumbar drainage (ELD) and shunt surgery. METHODS: The baseline levels of MD metabolites and ICP were monitored overnight in 40 consecutive patients with iNPH. In a subset of 28 patients, monitoring was continued during 3 days of ELD. Thirty-one patients received a ventriculoperitoneal shunt. The clinical severity of iNPH was determined before and then 3 and 6-12 months after shunt surgery. RESULTS: Altered levels of MD markers (lactate, pyruvate, lactate/pyruvate ratio, glutamate, and/or glycerol) were seen in all patients at baseline; these improved during ELD. Despite normal static ICP (mean ICP), the pulsatile ICP (the ICP wave amplitude) was increased in 24 patients (60%). Only the level of the ICP wave amplitude differentiated the ELD and/or shunt responders from nonresponders. CONCLUSIONS: The MD monitoring indicated low-grade cerebral ischemia in patients with iNPH; during ELD, cerebral metabolism improved. The pulsatile ICP (the ICP wave amplitude) was the only variable differentiating the clinical responders from the nonresponders. The authors suggest that the pulsatile ICP reflects the intracranial compliance and that CSF diversion improves the biophysical milieu of the nerve cells, which subsequently may improve their biochemical milieu.

Demonstration of uneven distribution of intracranial pulsatility in hydrocephalus patients.

OBJECT: Data from intracranial pressure (ICP) recordings in patients with hydrocephalus were reviewed to determine whether intracranial pulsatility within the cerebrospinal fluid (CSF) of cerebral ventricles (ICP(LV)) may differ from that within the brain parenchyma (ICP(PAR)), and whether pulsatility may differ between noncommunicating ventricles. METHODS: The authors retrieved data from recordings previously obtained in 7 patients with hydrocephalus (noncommunicating in 4 and communicating in 3) and shunt failure who received both an external ventricular drainage (EVD) and an ICP sensor as part of surveillance during intensive care. Simultaneous ICP(LV) and ICP(PAR) signals were available in 6 cases, and simultaneous signals from the lateral and fourth ventricles (ICP(LV) and ICP4V, respectively) were recorded in 1 case. The recordings with both signals were parsed into 6-second time windows. Pulsatility was characterized by the wave amplitude and rise time coefficient, and differences in pulsatility between the ICP(LV) and ICP(PAR) signals (6 cases) or ICP(LV) and ICP4V signals (1 case) were determined. RESULTS: There was uneven distribution of intracranial pulsatility in all 7 patients, shown as significantly elevated pulsatility (that is, higher wave amplitudes and rise time coefficients) within the ventricles (ICP(LV)) than within brain parenchyma (ICP(PAR)) in 6 patients, and significantly higher pulsatility in the fourth (ICP4V) than in the lateral (ICP(LV)) ventricles in 1 patient. Differences > or = 1 mm Hg in ICP wave amplitude were found in 0.5-100% (median 9.4%) of observations in the 7 patients (total number of 6-second time windows, 68,242). CONCLUSIONS: The present observations demonstrate uneven distribution of intracranial pulsatility in patients with hydrocephalus, higher pulse pressure amplitudes within the ventricular CSF (ICP(LV)) than within the brain parenchyma (ICP(PAR)). This may be one mechanism behind ventricular enlargement in hydrocephalus.

Differential effects of osmotherapy on static and pulsatile intracranial pressure.

OBJECTIVE: A bolus infusion of 7.2% saline in 6% hydroxyethyl starch 200/0.5 (HS) attenuates static intracranial pressure (mean ICP) in subarachnoid hemorrhage patients. This study addressed how HS affects intracranial pulsatility, which is more indicative of intracranial compliance than static ICP. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Intensive care unit in a university hospital. PATIENTS: Sedated and mechanically ventilated patients suffering from spontaneous subarachnoid hemorrhage. INTERVENTIONS: Twenty patients received an infusion of HS, mean 1.5 mL/kg. Static ICP was characterized by mean ICP and intracranial pulsatility by mean ICP wave amplitude, both parameters determined simultaneously during consecutive 6-sec time windows. We compared average values of these parameters during 15-min periods just before the infusion and after maximum effect was reached. MEASUREMENTS AND MAIN RESULTS: Mean ICP wave amplitude decreased 3.4 mm Hg from a baseline of 9.8 mm Hg, p < 0.0001. However, even though a target level of <15 mm Hg was reached for mean ICP in 65% of interventions, the target of <5 mm Hg for mean ICP wave amplitude was reached in only 30% of interventions. We found no correlation between changes in mean ICP wave amplitude and mean systemic arterial blood pressure wave amplitude, p = 0.27. CONCLUSIONS: The results confirm that osmotherapy attenuates both static ICP (mean ICP) and pulsatile ICP (mean ICP wave amplitude). Most importantly, however, during the majority of HS infusions, the target value of mean ICP wave amplitude was not reached even though the targets for mean ICP and mean cerebral perfusion pressure were reached. This suggests that the intracranial compliance state was still unfavorable even though mean ICP and mean cerebral perfusion pressure had reached normal ranges. The reduction in intracranial pulsatility could not be explained by attenuation in arterial pulsatility because there was no correlation between ICP and arterial blood pressure wave amplitudes.