Surgical management of acute subdural haematomas: current practice patterns in the United Kingdom and the Republic of Ireland.

INTRODUCTION: Uncertainty remains as to the role of decompressive craniectomy (DC) for primary evacuation of acute subdural haematomas (ASDH). In 2011, a collaborative group was formed in the UK with the aim of answering the following question: "What is the clinical- and cost-effectiveness of decompressive craniectomy, in comparison with craniotomy for adult patients undergoing primary evacuation of an ASDH?" The proposed RESCUE-ASDH trial (Randomised Evaluation of Surgery with Craniectomy for patients Undergoing Evacuation of Acute Subdural Haematoma) is a multicentre, pragmatic, parallel group randomised trial of DC versus craniotomy for adult head-injured patients with an ASDH. In this study, we used an online questionnaire to assess the current practice patterns in the management of ASDH in the UK and the Republic of Ireland, and to gauge neurosurgical opinion regarding the proposed RESCUE-ASDH trial. MATERIALS AND METHODS: A questionnaire survey of full members of the Society of British Neurological Surgeons and members of the British Neurosurgical Trainees Association was undertaken between the beginning of May and the end of July 2012. RESULTS: The online questionnaire was answered by 95 neurosurgeons representing 31 of the 32 neurosurgical units managing adult head-injured patients in the UK and the Republic of Ireland. Forty-five percent of the respondents use primary DC in at least 25% of patients with ASDH. In addition, of the 22 neurosurgical units with at least two Consultant respondents, only three units (14%) showed intradepartmental agreement regarding the proportion of their patients receiving a primary DC for ASDH. CONCLUSION: The survey results demonstrate that there is significant uncertainty as to the optimal surgical technique for primary evacuation of ASDH. The fact that the majority of the respondents are willing to become collaborators in the planned RESCUE-ASDH trial highlights the relevance of this important subject to the neurosurgical community in the UK and Ireland.

Temporal trends in head injury outcomes from 2003 to 2009 in England and Wales.

BACKGROUND: Case fatality rates after blunt head injury (HI) did not improve in England and Wales between 1994 and 2003. The United Kingdom National Institute of Clinical Excellence subsequently published HI management guidelines, including the recommendation that patients with severe head injuries (SHIs) should be treated in specialist neuroscience units (NSU). The aim of this study was to investigate trends in case fatality and location of care since the introduction of national HI clinical guidelines. METHODS: We conducted a retrospective cohort study using prospectively recorded data from the Trauma and Audit Research Network (TARN) database for patients presenting with blunt trauma between 2003 and 2009. Temporal trends in log odds of death adjusted for case mix were examined for patients with and without HI. Location of care for patients with SHI was also studied by examining trends in the proportion of patients treated in non-NSUs. RESULTS: Since 2003, there was an average 12% reduction in adjusted log odds of death per annum in patients with HI (n=15,173), with a similar but smaller trend in non-HI trauma mortality (n=48,681). During the study period, the proportion of patients with HI treated entirely in non-NSUs decreased from 31% to 19%, (p <0.01). INTERPRETATION: The reduction in odds of death following HI since 2003 is consistent with improved management following the introduction of national HI guidelines and increased treatment of SHI in NSUs.

Modulating effect of apolipoprotein E polymorphisms on secondary brain insult and outcome after childhood brain trauma.

OBJECTIVE: The aim of this study was to determine the relationship between apolipoprotein E (APO E) alleles, the amount of cerebral perfusion pressure (CPP) insult and outcome in children after brain trauma. MATERIALS AND METHODS: In a prospective two-centre case-control study, the APO E genotypes of 65 critically ill children admitted after brain trauma were correlated with age-related CPP insult quantification, conscious state at the time of discharge from intensive care and global outcome at 6 months post-injury. One hundred sixty healthy age- and sex-matched children were genotyped as controls. RESULTS: The CPP insult level among the e4 carriers with poor outcome was significantly less than the non-e4 carriers (p=0.03). Homozygotic e3 patients with good recovery did so despite having suffered nearly 26 times more CPP insult than those who were not e3 homzygous (p=0.02). CONCLUSION: Different APO E alleles may potentially affect cerebral ischaemic tolerance differently in children after brain trauma.

The measurement of brain tissue stiffness in-vivo.

BACKGROUND: There is considerable interest in surgical decompression as a management strategy (RescueICP) for intractable intracranial hypertension. After such an operation measurements of intracranial pressure (ICP) and thus cerebral perfusion pressure (CPP) become less meaningful. Measurements of the biomechanical properties of the brain may be one measure capable of detecting changing status of such patients. However these properties of the brain are neither documented or well understood. We have developed an indentation probe capable of making measurements of human brain stiffness. METHOD: The device consists of an indenting tip of depth 2 mm and diameter 12 mm surrounded by an annular body of 20 mm diameter. Measurements are made by two load cells, connected through interface electronics to a laptop computer. FINDINGS: Laboratory measurements show the probe to provide accurate and repeatable measurements over a range of zero to 10N. Inter-operator variability from six healthcare professionals had a coefficient of variance of 8.75%. Measurements obtained during surgery from a patient undergoing tumour resection were towards the lower end of the device's measurable range. CONCLUSIONS: We have determined that this indentation device has a linear response and that the inter- and intra-operator variability is low. Although the device is still in an early stage of development, preliminary results during intracranial surgery demonstrate that this device is capable of measuring in-vivo tissue stiffness. Further work is required to derive a quantitative "stiffness index" from the two load curves. In addition a standard operation method is required so that consistent and repeatable measurements are made. The device may be of value in assessing patients after decompressive craniectomy.

Lumbar subcutaneous shunt: a novel technique for therapeutic decision making in normal pressure hydrocephalus (NPH) and benign intracranial hypertension (BIH).

Selecting patients who will benefit from a permanent CSF diversion procedure in benign intracranial hypertension (BIH) or communicating hydrocephalus due to normal pressure hydrocephalus (NPH) has inherent problems. The percutaneous introduction of a lumbar subcutaneous shunt (LSS) under local anaesthesia facilitates both a prolonged CSF drainage under aseptic conditions and also elicits an adequate clinical response. We describe the technique of a lumbar subcutaneous shunt and our experience with its use in patients with BIH and NPH. Postprocedure changes in the patients' clinical status were noted. Patients with a transient clinical improvement underwent a subsequent definitive CSF diversion; those with a sustained clinical improvement or no change in symptoms had no further procedure.

The effect of the results of the STICH trial on the management of spontaneous supratentorial intracerebral haemorrhage in Newcastle.

Recently, the Surgical Trial in IntraCerebral Haemorrhage (STICH) was unable to show an overall benefit from 'early surgery' compared with a policy of 'initial conservative treatment'. Here, we evaluated the impact of the STICH results on the management of spontaneous supratentorial intracerebral haemorrhage (ICH) in the Newcastle upon Tyne Hospitals. The STICH results were released to the Neurosurgery Department at Newcastle General Hospital in November 2003; using ICD-10 data, we analysed ICH admissions before (2002) and after (2004, 2006, 2007) this. We assessed numbers of Neurosurgery and Stroke Unit admissions, numbers of clot evacuation procedures, and 30-day mortality rate (Neurosurgery vs. Stroke Unit admissions). Subarachnoid haemorrhage (SAH) admissions data were also collected to corroborate our findings. There were 478 spontaneous supratentorial ICH admissions in total; 156 in 2002, 120 in 2004, 106 in 2006 and 96 in 2007. SAH admissions remained remarkably constant over this period. Neurosurgery admissions decreased significantly across the four time periods, from 71% of total ICH admissions (n = 156) in 2002 to 55% (n = 96) in 2007, and Stroke Unit admissions increased significantly from 8% (n = 156) in 2002 to 30% (n = 96) in 2007 (chi(2) = 20.968, p < 0.001, df = 3). Clot evacuation procedures also decreased significantly from 32% (n = 111) of Neurosurgery admissions in 2002 to 17% (n = 53) in 2007 (chi(2) = 11.919, p = 0.008, df = 3). 30-day mortality increased in Neurosurgery from 14% of Neurosurgery admissions (n = 111) in 2002 to 26% (n = 53) in 2007, and decreased in the Stroke Unit, from 42% of Stroke Unit admissions (n = 12) in 2002 to 17% (n = 29) in 2007. The STICH results have significantly impacted ICH management in Newcastle, with a trend towards fewer Neurosurgery admissions and clot evacuations, and increased Stroke Unit admissions. The role of surgery for ICH remains controversial, and randomization continues in STICH II for patients with superficial lobar ICH.

The prognostic value of serum S-100B protein in spontaneous subarachnoid haemorrhage.

BACKGROUND: Despite the major progress in neurophysiological monitoring, there are still difficulties in the early identification and quantification of cerebral damage after a stroke. In this prospective study we examined the associations between serum S-100B protein, a serum marker of brain injury, and initial neurological-neuroimaging severity, secondary deterioration, external ventricular drainage (EVD: therapeutic intervention) and outcome in patients with subarachnoid haemorrhage (SAH). METHOD: We recorded all pertinent clinical data of 52 patients with SAH and measured S-100B serum levels on admission and every 24 h for a maximum of 9 consecutive days. Mann-Whitney U-test and Kruskal Wallis analysis were employed to assess the association of S-100B levels with all variables of interest. Log-rank test was used to evaluate survival and Cox's proportional hazard regression analysis to define the significant predictors of survival rate. FINDINGS: Admission S-100B was statistically significantly associated with initial neurological status, neuroimaging severity, and one-year outcome (p = 0.0002, 0.001, and 0.017, Kruskal Wallis analysis). Admission S-100B above 0.3 microg/L predicted unfavourable outcome (p < 0.0001, log rank test) and constituted an independent predictor of short-term survival (p = 0.035 Cox's proportional hazard regression analysis) with a hazard ratio of 2.2 (95% C.I.: 1.06-4.6) indicating a more than doubling of death probability. Secondary neurological deterioration associated with S-100B increase (p < 0.0001) and external ventricular drainage (EVD) with S-100B reduction (p = 0.003, Wilcoxon signed rank test). CONCLUSIONS: Serum S-100B protein seems to be a useful biochemical indicator of neurological - neuroimaging severity, secondary deterioration, EVD (therapeutic intervention), and outcome in patients with SAH.

Intraventricular hemorrhage and hydrocephalus after spontaneous intracerebral hemorrhage: results from the STICH trial.

INTRODUCTION: Intraventricular hemorrhage (IVH), either independent of or as an extension of intracranial bleed, is thought to carry a grave prognosis. Although the effect of IVH on outcome in patients with subarachnoid hemorrhage has been extensively reviewed in the literature, reports of spontaneous intracerebral hemorrhage (ICH) in similar situations have been infrequent. The association of hydrocephalus in such situations and its influence on outcome is also uncertain. PATIENTS AND METHODS: As a sub-analysis of data obtained through the international Surgical Trial in Intracerebral Hemorrhage (STICH), the impact of IVH, with or without the presence of hydrocephalus, on outcome in patients with spontaneous ICH was analyzed. CT scans of randomized patients were examined for IVH and/or hydrocephalus. Other characteristics of hematoma were evaluated to see if they influenced outcome, as defined by the STICH protocol. RESULTS: Favorable outcomes were more frequent when IVH was absent (31.4% vs. 15.1%; p < 0.00001). The presence of hydrocephalus lowered the likelihood of favorable outcome still further to 11.5% (p = 0.031). In patients with IVH, early surgical intervention had a more favorable outcome (17.8%) compared to initial conservative management (12.4%) (p = 0.141). CONCLUSION: The presence of IVH and hydrocephalus are independent predictors of poor outcome in spontaneous ICH. Early surgery is of some benefit in those with IVH.

The significance of crossovers after randomization in the STICH trial.

INTRODUCTION: Of all forms of stroke, spontaneous intracerebral haemorrhage (ICH) causes the highest morbidity and mortality. The Surgical Trial in Intracerebral Haemorrhage (STICH) found no difference in outcomes between patients randomized to surgical or conservative treatment. PATIENTS AND METHODS: Of 530 patients randomized to initial conservative treatment, 140 crossed over to surgery. This study examines the variables associated with crossover. RESULTS: Dominant features of the crossover group were: male, (p = 0.04), right-sided clot (p = 0.03), lobar clot (p = 0.003), clot volume (median 64 mL for crossovers vs. 38 mL for others, p < 0.00001), midline shift (median 6 mm for crossovers vs. 3 mm for others, p < 0.00001), superficial clot (median 1.3 mm for crossovers vs. 11.5 mm for others, p < 0.00001), and randomization within 12 hours of ictus (p < 0.0005). Thalamic location (p = 0.002) was under-represented. Intraventricular haemorrhage, hydrocephalus, and focal deficits were not associated with crossover. Craniotomy was the method of evacuation in 85% of crossover patients. CONCLUSIONS: Crossover to surgery was more likely when ICH had these features: Right side, lobar location, superficial, large volume, big shift, and early randomization. Crossovers formed a worse prognostic group compared to non-crossovers. Surgery did not affect trial results, which were analyzed by intention-to-treat.

Decompressive craniectomy in traumatic brain injury: the randomized multicenter RESCUEicp study (www.RESCUEicp.com).

The RESCUEicp (Randomized Evaluation of Surgery with Craniectomy for Uncontrollable Elevation of intracranial pressure) study has been established to determine whether decompressive craniectomy has a role in the management of patients with traumatic brain injury and raised intracranial pressure that does not respond to initial treatment measures. We describe the concept of decompressive craniectomy in traumatic brain injury and the rationale and protocol of the RESCUEicp study.

Clinical comparison of tympanic membrane displacement with invasive ICP measurements.

OBJECTIVE: Tympanic membrane displacement (TMD) measurements may be useful in the management of patients with hydrocephalus if they can be directly associated with measurements of ICP. We have compared TMD measurements using the Marchbanks Measurement System with invasive ICP monitoring. METHODS: Twenty-nine patients who were undergoing routine invasive monitoring using a Camino fibre optic ICP measurement system as part of their clinical management were studied. Simultaneous measurements of ICP and TMD in both sitting and supine positions were successfully made in thirteen patients. RESULTS: Thirty-nine pairs of readings were obtained. The invasive ICP readings varied from 1 to 36 mmHg in the supine position and from -12 to +35 mmHg sitting. Corresponding TMD values varied from 275 to +277 nL in the supine position and -133 to +466 nL sitting. Linear regression showed a significant negative relationship between the two measurements (r = -0.57, p = 0.0013). CONCLUSIONS: There is a strong negative linear association between mean TMD and invasively measured ICP and this relationship is highly significant. Nevertheless, TMD is a poor surrogate for ICP in clinical terms because the predictive limits of the linear regression are too wide. However, serial intra-patient measurements may be useful to determine changes in ICP with time.

Which paediatric head injured patients might benefit from decompression? Thresholds of ICP and CPP in the first six hours.

Severe head injury in childhood continues to be associated with considerable mortality and morbidity. Early surgical decompression may be beneficial and the objective of this study was to examine the relationship between age-related thresholds of mean intracranial pressure (ICP) and cerebral perfusion pressure (CPP) over the first 6 hours and age outcome in paediatric head injury patients. A total of 209 head injured children admitted to five UK hospitals were studied. Patients aged 2 to 16 years were included if they had a minimum of six hours of invasive pressure monitoring. Mean values of ICP and CPP over this period were calculated and compared to those with independent (good recovery and moderate disability) and poor outcome (severe disability, and death) for different age groups. There were 148 children with independent outcome (92 good recovery, 56 moderately disabled), and 61 with poor outcome (30 severely disabled, 31 deaths). There was a significant difference between those with independent compared to poor outcome in relation to ICP (p < 0.001) and CPP (p < 0.001). Patients were divided into three groups according to age. The sensitivity of ICP and CPP in predicting outcome was similar for all groups but the specificity differed between groups. At a CPP of 50 mmHg the specificity varied between the age groups (2 to 6 years: 0.47, 7 to 10 years: 0.28 and 11 to 16 years: 0.10) and similarly for an ICP of 25 mmHg (2 to 6 years: 0.53, 7 to 10 years: 0.44 and 11 to 16 years: 0.38). Younger children may be able to tolerate lower perfusion pressures and still have an independent outcome. Our threshold values for young children are likely to be important in the identification of patients who might benefit from new treatments such as surgical decompression.

Quantification of secondary CPP insult severity in paediatric head injured patients using a pressure-time index.

This paper describes and validates a new Cumulative Pressure-Time Index (CPT) which takes into account both duration and degree of cerebral perfusion pressure (CPP) derangement and determines critical thresholds for CPP, in a paediatric head injury dataset. Sixty-six head-injured children, with invasive minute-to-minute intracranial pressure (ICP) and blood pressure monitoring, had their pre-set CPP derangement episodes (outside the normal range) identified in three childhood age-bands (2-6, 7-10, and 11-16 years) and global outcome assessed at six months post injury. The new cumulative pressure-time index more accurately predicted outcome than previously used summary measures and by varying the threshold CPP values, it was found that these physiological threshold values (< or = 48, < or = 52 and < or = 56 mmHg for 2-6, 7-10, and 11-16 years respectively) best predicted brain insult in terms of subsequent mortality and morbidity.

Clinical comparison of tympanic membrane displacement with invasive intracranial pressure measurements.

A non-invasive method of assessing intracranial pressure (ICP) would be of benefit to patients with abnormal cerebral pathology that could give rise to changes in ICP. In particular, it would assist the regular monitoring of hydrocephalus patients. This study evaluated a technique using tympanic membrane displacement (TMD) measurements, which has been reported to provide a reliable, non-invasive measure of ICP. A group of 135 hydrocephalus patients was studied, as well as 13 patients with benign intracranial hypertension and a control group of 77 volunteers. TMD measurements were carried out using the Marchbanks measurement system analyser and compared between the groups. In 36 patients, invasive measurements of ICP carried out at the same time were compared with the TMD values. A highly significant relationship was found between TMD and ICP but intersubject variability was high and the predictive value of the technique low. Taking the normal range of ICP to be 10-15 mmHg, the predictive limits of the regression are an order of magnitude wider than this and therefore Vm cannot be used as a surrogate for ICP. In conclusion, TMD measurements do not provide a reliable non-invasive measure of ICP in patients with shunted hydrocephalus.

Head injuries: a study evaluating the impact of the NICE head injury guidelines.

BACKGROUND: The NICE head injury guidelines recommend a different approach in the management of head injury patients. It suggests that CT head scan should replace skull x ray (SXR) and observation/admission as the first investigation. We wished to determine the impact of NICE on SXR, CT scan, and admission on all patients with head injury presenting to the ED setting and estimate the cost effectiveness of these guidelines, which has not been quantified to date. DESIGN: Study of head injury patients presenting to two EDs before and after implementation of NICE guidelines METHODS: The rate of SXR, CT scan, and admission were determined six months before and one month after NICE implementation in both centres. The before study also looked at predicted rates had NICE been applied. This enabled predicted and actual cost effectiveness to be determined. RESULT: 1130 patients with head injury were studied in four 1 month periods (two in each centre). At the teaching hospital, the CT head scan rate more than doubled (3% to 7%), the SXR declined (37% to 4%), while the admission rate more than halved (9% to 4%). This represented a saving of 3381 pounds sterling per 100 head injury PATIENTS: greater than predicted with no adverse events. At the District General Hospital, the CT head scan rate more than quadrupled (1.4% to 9%), the SXR dropped (19 to 0.57%), while the admission rate declined (7% to 5%). This represented a saving of 290 pounds sterling per 100 head injury patients: less than predicted. CONCLUSION: The implementation of the NICE guidelines led to a two to fivefold increase in the CT head scan rate depending on the cases and baseline departmental practice. However, the reduction in SXR and admission appears to more than offset these costs without compromising patient outcomes.

Experimental intracerebral mass: description of model, intracranial pressure changes and neuropathology.

In a rodent model designed to replicate the mass effects of spontaneous intracerebral hemorrhage, we have found that there is little change in intracranial pressure (ICP) with microballoons (25 microliters and 50 microliters in volume) equivalent in size to those lesions which occur with this disorder in man. With larger volumes (100 microliters) there is an increase in ICP which is associated with systemic effects on cerebral perfusion pressure (CPP). Neuropathological evidence of ischemic brain damage was found surrounding the mass in all animals, but this was independent of whether the mass was removed or not. These studies suggest that with a mass that corresponds to the size seen most commonly with spontaneous intracerebral hemorrhage in man, focal ischemic brain damage is produced without reduction in global CPP.

Surgery in intracerebral hemorrhage. The uncertainty continues.

BACKGROUND AND PURPOSE: Primary intracerebral hemorrhage (ICH) accounts for 10% to 20% of stroke but carries the highest rates of mortality and morbidity of all stroke subtypes. Current treatment, however, is varied and haphazard. The most recent Cochrane systematic review refers to 4 prospective, randomized controlled trials. We present a further meta-analysis to include 3 new trials. In addition, we review the trials of Chen et al and McKissock et al and discuss aspects of their quality that, we believe, prevent their inclusion in modern day meta-analysis. METHODS: Literature databases and articles were searched from 1966 to October 1999. Using the end points of death and dependency, the results of the 7 identified randomized trials were expressed as odds ratios. All available data were then analyzed with meta-analysis techniques. Analysis of relevant subsets of trials was also carried out. RESULTS: Meta-analysis of all 7 trials shows a trend toward a higher chance of death and dependency after surgery (OR 1.20; 95% CI 0.83 to 1.74). Meta-analysis was also carried out after exclusion of the Chen and McKissock trials for reasons discussed in the text. This meta-analysis suggests a benefit from surgery, with a reduction in the chances of death and dependency after surgical treatment by a factor of 0.63 (OR 0.63; 95% CI 0.35 to 1.14). CONCLUSIONS: When meta-analysis is restricted to modern-day, post-CT, well-constructed, balanced trials, a trend for surgery to reduce the chances of death and dependency is found. Perhaps, then, in the modern era of CT, good neuroanesthesia, intensive care, and the operating microscope, surgery has a role in the treatment of supratentorial intracerebral hemorrhage. The results of a large, multicenter, randomized controlled trial are urgently needed, and the ongoing International Surgical Trial of Intracerebral Hemorrhage should fulfill this objective.

Comparison of quantitative autoradiographic and xenon-133 clearance methods: correlation of gray and white matter cerebral blood flow with compartmental blood flow indices.

The relationships between CBF in gray and white matter to those of the fast and slow components of xenon-133 clearance curves remain uncertain. CBF was measured in 13 anaesthetized baboons under a variety of conditions, using both the xenon-133 clearance technique and [14C]iodoantipyrine quantitative autoradiography. There was a linear relationship between CBF, as determined by the stochastic (height/area) analysis of the clearance curve, and mean CBF determined from the autoradiograms (r = 0.94, p less than 0.001, slope = 0.86 +/- 0.09). There was also a linear correlation between the fast-flow component (measured with xenon-133) and blood flow in the cerebral gray matter (measured with [14C]iodoantipyrine) (r = 0.92, p less than 0.001, slope = 0.69 +/- 0.15) and between the slow-flow component (with xenon-133) and blood flow in white matter (with [14C]iodoantipyrine) (r = 0.79, p less than 0.01, slope = 0.81 +/- 0.10). In the primate brain, the fast- and slow-flow indices therefore appear to be representative of CBF in gray matter and white matter, respectively, whereas the stochastic analysis provides a stable measure of mean CBF within the tissue monitored.

Effect of the calcium antagonist nimodipine on local cerebral blood flow: relationship to arterial blood pressure.

The effect of the calcium antagonist nimodipine on local CBF in 31 regions of the CNS was studied with the [14C]iodoantipyrine autoradiographic technique in lightly anaesthetised, mechanically ventilated rats. Continuous intravenous infusion of nimodipine (1, 2, or 4 micrograms kg-1 min-1) produced a dose-dependent reduction in MABP (reduced by 26 +/- 2% after 30 min of nimodipine, 4 micrograms kg-1 min-1) and a significant elevation in plasma glucose concentration (increased by 44 +/- 2% after 30 min of nimodipine, 4 micrograms kg-1 min-1). Local CBF was increased significantly during infusions of nimodipine (1 microgram kg-1 min-1) in 9 of the 31 regions examined (including the cerebral cortex, hippocampus, hypothalamus, and most thalamic nuclei). In contrast to the increases in CBF observed in forebrain regions, no significant increases in CBF were observed during nimodipine infusions in regions of the lower brainstem, cerebellum, and pons or in myelinated fibre tracts. The proportionately greatest increases in local CBF were observed during infusions of the lowest dosage of nimodipine (1 microgram kg-1 min-1), suggesting either that this dosage provokes maximum cerebrovascular relaxation or that effects of increasing concentrations are counteracted by the concomitant systemic hypotension.

Effect of the calcium antagonist nimodipine on local cerebral blood flow and metabolic coupling.

The effects of a continuous infusion of the calcium antagonist nimodipine (1 microgram kg-1 min-1) on local CBF (LCBF) and local cerebral glucose utilisation (LCGU) were studied, using the quantitative autoradiographic [14C]iodoantipyrine and [14C]2-deoxyglucose techniques in 34 anatomically discrete regions of the brain in lightly restrained, conscious rats. The infusion of nimodipine at this concentration produced only a small (8%) reduction in the MABP. The administration of nimodipine did not alter the rate of glucose utilisation in any of the regions examined. By contrast, in 24 regions, CBF was increased significantly by 39-84% from control levels (for example, cerebral cortices, hippocampus, hypothalamus, and most thalamic nuclei). In vehicle-treated animals, there was an excellent correlation (p less than 0.01) between the local levels of CBF and glucose utilisation, with the ratio of flow to glucose use being approximately 1.5 ml mumol-1 in each brain region. During nimodipine treatment, there was a similarly excellent correlation (p less than 0.01) between LCBF and LCGU, but the median ratio between local flow and glucose use increased to 2.5 ml mumol-1.