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Objectives: Constant infusion lumbar infusion test (LIT) is an important way to find which patients, of those with signs and symptoms corresponding to normal pressure hydrocephalus (NPH) who will improve from shunt operation. LIT is a stress test on the ability for cerebrospinal fluid re-absorbtion. The aim of this study is to show how the information from LIT can be improved by quantitative analysis and avoidance of methodological pitfalls. Material and methods: The potential pitfalls, and the analysis method, are described in detail. The analysis was applied on pre-operative constant infusion LIT from 31 patients operated for NPH, with known outcome. The pre- and post-operative walking speed was used to grade pathology progression or improvement. Results: The maximal, plateau, intra-spinal pressure at constant infusion LIT is an ambivalent indicator for NPH: while low maximal pressure indicates no cerebrospinal fluid (CSF) absorbtion pathology, too high pressure (≥47 mmHg) may mean no diagnosis, because of stenosis of the Sylvian aqueduct. When subjects with too high intra-spinal pressure were excluded, the new analysis gave a couple of diagnostic volume parameters, of which one appears to be an optimal LIT parameter for identifying NPH patients with 14% better accuracy than plateau pressure. Conclusion: By avoiding methodological pitfalls, and optimal analysis of the results from lumbar infusion test, the number of NPH patients who do not have a successful outcome after shunt operation may be further decreased. (Less)

Objective: The physiological background for intracranial pressure, ICP, increase at brain compression is presently unknown. Current knowledge of the relationship between ICP and volume of brain compression is based on animal experiments, which has led to the theory of elastic brain tissue compression, which like a loaded spring causes the ICP increase. However, tests of brain tissue composition, or compression, find no basis for elasticity, or compression. The aim of this article is to describe the physiological features controlling ICP since it is necessary for the understanding of intracranial physiology, but also since ICP is an important parameter in neurointensive care medicine. Methods: This evaluation is based on the physiological consequences of the closed intracranial compartment, the thin-walled, compressible venous bed, the auto-regulation of cerebral blood flow, CBF, to blood pressure changes, and the coupling between ICP and the intra-capillary blood pressure through the thin, flexible capillary wall. These features influence the intracranial venous blood volume, the venous vascular resistance, and the CBF. Together these features are shown to revile the ICP dependence on the volume of brain volume compression. Results: The evaluation leads to a formula that describes the relationship between ICP and changes in the brain volume. The formula predicts an exponential ICP increase at brain compression like in animal experiments but, contrary to the elastic tissue theory, a gradually higher exponential for larger compression. Conclusion: The found relationship between ICP and changes in brain volume may prove to be a useful tool in neuro-intensive care patients for following changes in intracranial volumes by the aid of continuous ICP measurements. Since brain-compressing volumes includes the arterial pulse volume, the ICP formula may also enable CBF calculation from ICP measurements. The physiological relationships leading to the description of the relationship between ICP and brain volume change may by themselves help in understanding other intracranial phenomena, like ICP plateau-waves.

BACKGROUND: Patients with elevated intracranial pressure risk compromising their cerebral blood flow, resulting in ischemia. Lowering of the raised intracranial pressure, is therefore, mandatory. Reduction of the cerebral blood volume (CBV) might be target. In finding ways to do so, one has to be able to measure CBV. Measurement of CBV is, however, difficult. Radio(99mTc-)labeled erythrocytes (99mTcRBC) single photon emission computer-aided tomography (SPECT) is one established method used for CBV measurement. Recently, dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI), has also been successfully used for this purpose. The aim of this study was to validate the use of DSC-MRI for the measurement of CBV by the investigation of the correlation between the regional distributions of 99mTc-RBC SPECT and DSC-MRI measurement of CBV in humans. If possible, the aim was also to find a conversion constant that will enable the DCS-MRI to be interpreted as CBV (percent of brain volume). METHODS: CBV of 8 volunteers were studied under normocapnic and hypocapnic conditions. CBV was measured with both 99mTc-RBC SPECT and DSC-MRI. RESULTS: There were significant correlations between the regional distributions of CBV measured by 99mTc-RBC SPECT and DSC-MRI (rest: F=4.53, P

BACKGROUND: Recent studies in man have shown that cerebral blood flow increases during inhalation of nitrous oxide (N2O), a finding which is believed to be a result of an increased cerebral metabolic rate (CMR). However, this has not previously been evaluated in man. METHODS: Regional CMR(glu) (rCMR(glu)) was measured three dimensionally with positron emission tomography (PET) after injection of 2-(18F)fluoro-2-deoxy-D-glucose in 10 spontaneously breathing men (mean age 31 yr) inhaling either N2O 50% in O2 30% or O2 30% in N2. RESULTS: Global CMR(glu) in young men was 27 (3) micromol 100 g(-1) min(-1) [mean (SD)]. Inhalation of N2O 50% did not change global CMR(glu) [30 (5) micromol 100 g(-1) min(-1)] significantly, but it changed the distribution of the metabolism in the brain (P

Object. Intracerebral microdialysis has attracted increasing interest as a monitoring technique during neurological/neurosurgical intensive care. The purpose of this study was to compare cerebral energy metabolism, an indicator of secondary excitotoxic injury and cell membrane degradation close to focal traumatic lesions (“penumbra zones”) and in remote and apparently intact brain regions of the ipsilateral and contralateral hemispheres. Methods. The study included 22 consecutive patients with a mean age 44 ± 17 years and an estimated postresuscitation Glasgow Coma Scale motor score less than 5. Altogether 40 microdialysis catheters with radiopaque tips were inserted. Two catheters could not be localized on postoperative computerized tomography (CT) scans and were excluded from the analysis. The perfusates were analyzed at the patient's bedside for levels of glucose, pyruvate, lactate, glutamate, and glycerol with the aid of a CMA 600 Analyzer. The positions of eight (22%) of the 36 catheters were reclassified after a review of findings on CT scans. Except for pyruvate the values of all biochemical variables and the lactate/pyruvate (L/P) ratio were significantly different in the penumbra zone when compared with mean values found in “normal” tissue ipsilateral to the parenchymal damage and in contralateral normal tissue (p < 0.001). In the penumbra zone a slow normalization of the L/P ratio and levels of glutamate and glycerol were observed. In normal tissue these parameters remained within normal limits. Conclusions. Data obtained from intracerebral microdialysis can be correctly interpreted only if the locations of the catheters as they relate to focal brain lesions are visualized. A “biochemical penumbra zone” surrounds focal traumatic brain lesions. It remains to be proven whether therapeutic interventions can protect the penumbra zone from permanent damage.

Findings from 99mTc-HMPAO SPECT measurements at rest in a group of 19 school-age children with specific language impairment (SLI) were compared to a group of 12 children with attention-deficit hyperactivity disorder (ADHD). The regional cerebral blood flow (CBF) distributions were different in the two groups. Children with SLI showed significantly lower CBF values in the right parietal region and in the subcortical region compared to the ADHD group. In addition, the SLI group had symmetric CBF distributions in the left and right temporal regions, whereas the ADHD group showed the usual asymmetry with left-sided hemispheric predominance in the temporal regions. The findings give further evidence for anomalous neurodevelopment with deviant hemispheric lateralization as an important factor in the aetiology of SLI. They also point to the role of subcortical structures in language impairment in childhood. Earlier focus on cortical structures in SLI research needs to be widened to include subcortical regions as well.

Altered monoaminergic activity has earlier been associated with violent suicidal behaviour. In this study whole brain binding potential of the serotonin transporter (5HTT) and dopamine transporter (DAT) was measured by single photon emission computerised tomography (SPECT) in 12 patients after a serious suicide attempt and in 12 age, sex and season matched healthy controls. Clinical and temperamental assessments were analysed for possible associations with 5HTT and DAT. We found no significant 5HTT or DAT differences between patients and controls. In patients, but not in controls, there was a significant correlation between whole brain 5HTT and DAT. Impulsiveness according to the Marke Nyman Temperament (MNT) was significantly correlated to 5HTT in suicide attempters, but not in controls. Neither of the transporters could be regarded as a marker for serious suicidal behaviour. A previously discussed connection between serotonin and dopamine was replicated in this study. In suicide attempters, low 5HTT was associated with impulsivity and to some extent with depressive disorder-key factors for suicidal behaviour.

In patients with intracranial pathology, especially when comatose, it is desirable to have knowledge of the intracranial pressure (ICP). To investigate the relationship between ICP and transcranial Doppler (TCD) derived pulsatility index (PI) in neurosurgical patients, a prospective study was performed on patients admitted to our neurointensive care unit.Daily TCD mean flow velocity (mFV) measurements were made. TCD measurements were routinely performed bilaterally on the middle cerebral artery (MCA). PI (peak systolic-end diastolic velocities/mean flow velocity) was calculated.Eighty-one patients with various intracranial disorders who had an intraventricular catheter for registration of the ICP were investigated: 46 (57%) patients had subarachnoid hemorrhage, 21 (26%) patients had closed head injury, and 14 (18%) patients had other neurosurgical disorders. A total of 658 TCD measurements were made. ICP registrations were made parallel with all TCD measurements. A significant correlation (p0.0001) was found between the ICP and the PI with a correlation coefficient of 0.938: ICP = 10.93 x PI - 1.28. In the ICP interval between 5 to 40 mm Hg the correlation between ICP and PI enabled an estimation of ICP from the PI values with an SD of 2.5. The correlation between the cerebral perfusion pressure (CPP) and PI was significant (p0.0001) with a correlation coefficient of -0.493. When separating the measurements in severely elevated (120 cm/s) and subnormal (50 cm/s) TCD mFV values, the correlation coefficient between ICP and PI was 0.828 (p0.002) and 0.942 (p0.638), respectively.Independent of the type of intracranial pathology, a strong correlation between PI and ICP was demonstrated. Therefore, PI may be of guiding value in the invasive ICP placement decision in the neurointensive care patient.

� � � � � � � � � � � � � � � � Background: Little is known about the influence of racemic ketamine on autoregulation of cerebral blood flow (CBF), and available reports regarding its influence on cerebral hemodynamics are contradictory. This study was designed to evaluate cerebrovascular responses to changes in the mean arterial pressure (MAP) during ketamine anesthesia. Methods: In eight normoventilated pigs anesthesia was induced with propofol and maintained by i.v. infusion of ketamine (15.0 mg kg � 1 .h � 1 ) during measurements. The intra-arterial xenon clearance technique was used to calculate CBF. Balloon-tipped catheters were introduced in the inferior caval vein and mid-aorta, and increases or decreases by up to 40% in mean arterial pressure (MAP) in random order were achieved by titrated inflation of these balloon catheters. Cerebral blood flow was determined at each MAP level. Regression coefficients of linear pressure-flow curves were calculated in all animals. Results: From the mean baseline level (101 mmHg) MAP was reduced by 20% and 40%, and increased by 26% and 43% .T he maximal mean increase and decrease in MAP induced a 12% increase and a 15% decrease, respectively, of CBF from the

Arterial vasospasm after subarachnoid hemorrhage may cause cerebral ischemia. Treatment with hemodilution, reducing blood viscosity, and hypervolemia, increasing cardiac performance and distending the vasospastic artery, are clinically established methods to improve blood flow through the vasospastic arterial bed. Eight patients with transcranial Doppler verified vasospasm after subarachnoid hemorrhage were investigated with global (two-dimensional 133Xenon) and regional (three-dimensional 99 mTc-HMPAO) cerebral blood flow (CBF) measurements, before and after 1/iso- and 2/hypervolemic hemodilution. Hematocrit was reduced to 0.28 from 0.36. Hypervolemia was achieved by increasing blood volume by 1100 ml. Isovolemic hemodilution increased global cerebral blood flow from 52.25±10.12 to 58.56±11.73 ml * 100 g−1 * min−1 (p

Background It is generally argued that variations in cerebral blood flow create concomitant changes in the cerebral blood volume (CBV). Because nitrous oxide (N(2)O) inhalation both increases cerebral blood flow and may increase intracranial pressure, it is reasonable to assume that N(2)O acts as a general vasodilatator in cerebral vessels both on the arterial and on the venous side. The aim of the current study was to evaluate the effect of N(2)O on three-dimensional regional and global CBV in humans during normocapnia and hypocapnia. Methods Nine volunteers were studied under each of four conditions: normocapnia, hypocapnia, normocapnia + 40-50% N(2)O, and hypocapnia + 40-50% N(2)O. CBV was measured after (99m)Tc-labeling of blood with radioactive quantitative registration via single photon emission computer-aided tomography scanning. Results Global CBV during normocapnia and inhalation of 50% O(2) was 4.25 +/- 0.57% of the brain volume (4.17 +/- 0.56 ml/100 g, mean +/- SD) with no change during inhalation of 40-50% N(2)O in O(2). Decreasing carbon dioxide (CO(2)) by 1.5 kPa (11 mmHg) without N(2)O inhalation and by 1.4 kPa (11 mmHg) with N(2)O inhalation reduced CBV significantly (F = 57, P < 0.0001), by 0.27 +/- 0.10% of the brain volume per kilopascal (0.26 +/- 0.10 ml x 100 g(-1) x kPa(-1)) without N(2)O inhalation and by 0.35 +/- 0.22% of the brain volume per kilopascal (0.34 +/- 0.22 ml x 100 g(-1) x kPa(-1)) during N(2)O inhalation (no significant difference). The amount of carbon dioxide significantly altered the regional distribution of CBV (F = 47, P < 0.0001), corresponding to a regional difference in Delta CBV when CO(2) is changed. N(2)O inhalation did not significantly change the distribution of regional CBV (F = 2.4, P = 0.051) or Delta CBV/Delta CO(2) in these nine subjects. Conclusions Nitrous oxide inhalation had no effect either on CBV or on the normal CBV-CO(2) response in humans.

Total and regional cerebral glucose metabolism (CMRgl) was measured by positron emission tomography with 2-((18)F) fluoro-2-deoxy-D-glucose ((18)FDG) in 20 term infants with hypoxic ischemic encephalopathy (HIE) after perinatal asphyxia. All infants had signs of perinatal distress, and 15 were severely acidotic at birth. Six infants developed mild HIE, twelve moderate HIE, and two severe HIE during their first days of life. The positron emission tomographic scans were performed at 4-24 d of age (median, 11 d). One hour before scanning, 2-3.7 MBq/kg (54-100 microCi/kg) (18)FDG was injected i.v. No sedation was used. Quantification of CMRgl was based on a new method employing the glucose metabolism of the erythrocytes, requiring only one blood sample. In all infants, the most metabolically active brain areas were the deep subcortical parts, thalamus, basal ganglia, and sensorimotor cortex. Frontal, temporal, and parietal cortex were less metabolically active in all infants. Total CMRgl was inversely correlated with the severity of HIE (p0.01). Six infants with mild HIE had a mean (range) CMRgl of 55.5 (37.7-100.8) micromol.min(-1).100 g(-1), 11 with moderate HIE had 26.6 (13.0-65.1) micromol.min(-1).100 g(-1), and two with severe HIE had 10.4 and 15.0 micromol.min(-1).100 g(-1), respectively. Five of six infants who developed cerebral palsy had a mean (range) CMRgl of 18.1 (10.2-31.4) micromol.min(-1).100 g(-1) compared with 41.5 (13.0-100.8) micromol.min(-1).100 g(-1) in the infants with no neurologic sequela at 2 y. We conclude that CMRgl measured during the subacute period after perinatal asphyxia in term infants is highly correlated with the severity of HIE and short-term outcome.

PURPOSE: To compare chemotherapy treatment monitoring in astrocytoma by 201thallium single photon emission computed tomography (SPECT) and photon magnetic resonance spectroscopy (1H-MRS) with magnetic resonance imaging (MRI), and to evaluate the influence of morphological tumor changes on cerebral 201thallium uptake and metabolic changes in 1H-MRS. MATERIALS AND METHODS: Six patients with highly malignant astrocytomas were followed with quantitative 201thallium SPECT, MRI, and 1H-MRS during chemotherapy. Maximum follow-up included six examinations per patient by either method during 18 months. Criteria were set for: (1) regression (> or = 25% tumor reduction), (2) status quo ( or = 25% tumor increase). Results were compared with the clinical state of disease. Changes of tumor volume, contrast enhancement, necrosis, hemorrhage and edema on MRI were compared to changes in 201thallium uptake volumes and 1H-MRS metabolite ratios. RESULTS: Six patients were followed with a total of twenty-four examinations with 201thallium SPECT, MRI and 1H-MRS, respectively, between February 1997 and October 1998. Five patients developed clinical progression of disease, 4 out of 5 cases showed SPECT progression, 4 out of 5 cases MRI progression, and 1 out of 2 interpretable cases 1H-MRS progression at final assessment before clinical deterioration. During the phase of clinically stable disease; (A) the criterion for regression or status quo was met in 10 out of 13 assessments with SPECT, 11 out of 13 with MRI, and 8 out of 9 interpretable 1H-MRS; (B) the criterion for progression was met in 3 out of 13 with SPECT, 2 out of 13 with MRI, and 1 out of 9 interpretable 1H-MRS. The accuracy of SPECT, MRI, and 1H-MRS in identifying changes of tumor burden concordant with patients' clinical course was 78%, 83%, and 82%, respectively. SPECT regression was associated with MRI decrease of tumor size, contrast enhancement, edema and hemorrhage. SPECT progression was associated with MRI increase of the same parameters and the increase of necrosis. 1H-MRS regression was associated with decrease of edema. 1H-MRS progression was associated with increase of tumor size, hemorrhage, and increase or decrease of contrast enhancement. CONCLUSIONS: Both 201thallium SPECT and 1H-MRS evaluation showed sensitivity for detection of astrocytoma progression. We did not find a higher accuracy of SPECT or MRS than of MRI in astrocytoma chemotherapy monitoring. Treatment induced MRI changes were associated with 201thallium uptake variations. 1H-MRS was difficult to apply for astrocytoma treatment monitoring. Improvements regarding size of measurement area such as multivoxel MRS and fat suppression pulses appeared desirable, and also the use of functional techniques with superior resolution such as dual isotope SPECT. However, our results suggest that 201thallium SPECT and 1H-MRS can provide additional information to MRI for chemotherapy efficacy evaluation in selected cases. (Less)

We prospectively studied a cohort of 25 HIV-1 infected individuals with no clinical signs of encephalopathy with 99mTc-HMPAO-SPECT. The findings were correlated with magnetic resonance imaging (MRI), neuropsychological testing and clinical staging aiming at the early diagnosis of HIV encephalopathy by single photon emission computed tomography (SPECT). A total of 25 matched seronegative controls were subject to neuropsychological testing only. A total of 24 patients and controls were monitored for 6-46 months (mean and median 26 months). No patients developed AIDS dementia complex during the study; 3 patients developed minimal symptoms (MSK classification stage 0.5). There was a significant decline in 99mTc-HMPAO uptake over time and neuropsychological abnormalities progressed. Unexpectedly, there was a correlation of high cortical and subcortical 99mTc-HMPAO uptake and low performance in cognitive dysfunction tests, indicating a possible inflammatory reaction in the brain with increased blood flow due to HIV infection. We conclude that, in non-demented HIV-infected individuals, both the 99mTc-HMPAO uptake and functional level slowly decrease over time, but the regional cerebral blood flow decrease could be masked by a direct HIV-induced inflammatory reaction in the brain, which gives a 99mTc-HMPAO hyperfixation.

Astra (S)-3-[ 123 I]iodo-5,6-dimethoxyl-N-[(I-ethyl-2-pyrrolidinyl)methyl]-salicylarnide ( 123 I-NCQ298) is a new high-affinity D2-receptor ligand for use in single photon emission tomography (SPET) studies. We have studied the biodistribution and absorbed radiation dose of 123 I-NCQ298 in humans. The mean effective dose for adults was 0.055 mSv MBq -1 . Brain uptake and clearance was measured with a head dedicated SPET camera. 123 I-NCQ298 showed specific uptake in the basal ganglia with a low clearance rate (time constant of 9-34 h). The extrastriatal binding was variable (average 30%, maximum 60% of that in the basal ganglia at 1 h), but with a clearance rate twice that of the basal ganglia. The fairly high level of extrastriatal binding precluded the use of a quotient between the basal ganglia and cerebellum-to-frontal cortex 123 I-NCQ298 concentration as a measure for basal ganglia D2-receptor density. Chronic schizophrenic patients treated with conventional neuroleptics had a decreased affinity for 123 I-NCQ298 in the basal ganglia in the range 10-60% of the median value for the control, untreated subjects.

The aim of the study was to evaluate whether or not dipole analysis of extracranially recorded epileptiform activity, using a spherical three-shell head model, may distinguish epilepsy of mesolimbic origin from origins of other locations. Dipole analysis was performed on previously extracranially recorded interictal epileptiform discharges in 22 patients investigated for ictal onset patterns with subdural electrodes over one or both subtemporal areas. The dipole results in two groups of patients were compared. Group A contained patients in whom the subdural investigation showed subtemporal seizure onset (indicating mesolimbic epilepsy) ipsilateral to the dipole locations. Group B contained patients in whom seizure onset was other than ipsilateral subtemporal, or in whom seizure onset could not be determined. Group A patients had uniform dipole results, with an oblique posterior, slightly elevated dipole orientation, and an anterior temporal dipole location. Group B patients had more variable dipole results. If dipoles with anterior temporal location, and oblique posterior and elevated orientation are obtained, epilepsy of mesolimbic origin should be suspected. If the dipole locations or orientations markedly deviate from this pattern, the epileptogenic region is likely to be other than mesolimbic.

Nitrous oxide and isoflurane have different effects on absolute cerebral blood flow (CBF) and regional distribution of CBF in humans. In this study we examined the effects of isoflurane in combination with nitrous oxide on CBF. We studied 10 patients (two groups of five patients, ASA I) anaesthetized with 50% nitrous oxide and either 0.5 or 1.0 MAC of isoflurane during normocapnia (PaCO2 5.7 kPa) using two-dimensional CBF measurement (CBFxenon) (i.v. 133xenon washout technique) and a three-dimensional method for measurement of regional CBF (rCBF) distribution with SPECT (single photon emission computer-aided tomography with 99mTc- HMPAO). The results were compared with 1.0 MAC of isoflurane from a previous study performed in exactly the same way as the present investigation. During normocapnia, anaesthesia with 50% nitrous oxide and 0.5 MAC of isoflurane resulted in a mean CBFxenon of 45 (SEM 5) ISI units. Increasing the isoflurane concentration to 1.0 MAC had no significant effect on mean CBFxenon (53 (5) ISI units). Both flow values were significantly (P = 0.01) higher than the CBFxenon value obtained when 1 MAC of isoflurane was administered alone (33 (3) ISI units). There were no significant differences in rCBF distribution regardless of whether or not isoflurane was given alone or together with nitrous oxide at 0.5 or 1 MAC. In all situations there were higher relative flows in subcortical regions (thalamus and basal ganglia, 10%) and in the pons (7-10% above average). rCBF in the cerebellum was approximately 10% greater than average. In summary, we have found that mean CBF was greater with combined nitrous oxide and isoflurane anaesthesia than previously found with isoflurane alone; however, relative flow distribution was similar.

A brief review of the role of SPECT (single photon emission computed tomography) in the diagnosis of dementing brain disease is given. Between 1990 and 1995 some 100 original articles deal with SPECT measurements with radioactive tracers of brain function in demented patients. The main field is measurement of regional cerebral blood flow (rCBF) but there is an increasing number of studies concerning receptor functions in the demented brain.

BackgroundThis study examines relations between regional cerebral blood flow (rCBF) and neuropsychological test results, age at onset and duration of disease in patients with frontotemporal-type dementia (FTD).MethodSixteen patients with a diagnosis of probable FTD were examined using single photon emission computerised tomography (SPECT) with 99mTc-HMPAO as the tracer. The rCBF of 14 regions of interest relative to cerebellar blood flow was calculated. Psychological tests assessing language, verbal fluency, memory and visuospatial constructive ability were given.ResultsCorrelations were demonstrated between a global impairment score and relative blood flow in lateral frontal, medial frontal and left orbital frontal areas. Verbal fluency scores correlated with left lateral frontal medial frontal and left anterior inferior temporal blood flow. No relationships between decrease in CBF and age at onset or duration of disease, or between impaired cognitive function and age at onset or duration of disease, were found.ConclusionsThe present study demonstrates a close coupling between reduced rCBF and specific neuropsychological deficits in FTD.

Ten patients with complex partial epileptic seizures undergoing invasive video/EEG-monitoring were recorded with a combination of 10 subdural strip electrode contacts (subtemporal + lateral temporal), and 22 extracranial recording sites. In each patient several spikes with different intracranial distributions were identified, and spikes with similar distributions were averaged together with their extracranial activity. Dipole analysis of the extracranial activity was performed with the BESA® program (Scherg, Garching Instrumente, Munchen). In the horizontal plane subtemporal spikes gave oblique posterior, and lateral temporal spikes straight lateral or oblique anterior dipole orientations. In the coronal plane all spikes had an elevated orientation, most pronounced for medial subtemporal spikes. Dipole locations did not separate as well as dipole orientations. In our opinion our results would be difficult to explain without postulating a substantial degree of volume conduction from deep temporal areas to the surface. We conclude that dipole analysis of the interictal epileptiform activity does provide substantial information about which parts of the temporal lobe are involved in the epileptogenic process, making the method a useful tool in the preoperative investigation of patients with drug resistant partial epilepsy.

Three patients, two women and one man, aged 56-70 year (mean 59 years) with modest neurological deficits and bilateral occlusion of the common carotid arteries initially identified by duplex scanning and angiography were followed by repeated clinical and transcranial Doppler examination (TCD) over 6.5 years. Vasomotor reactivity (VMR) was tested by combined examination of TCD and xenon-133 cerebral blood flow (CBF) before and after intravenous administration of 1 g acetazolamide. At follow-up CBF was measured using single photon emission computerised tomography (SPECT). In two patients mean velocities in the middle cerebral artery (MCA) were within the normal range at repetitive examinations with good VMR ranging 30-111%, whereas CBF was reduced in MCA territories ranging 29-36 ml 100 g(-1) min(-1), but increasing 44-69% after acetazolamide, indicating good VMR. These 2 cases had anterograde flow in the ophthalmic artery and siphon. The third patient had very low MCA mean velocities of 21-27 cm sec(-1), increasing 26-33% after acetazolamide. This patient had retrograde flow in the ophthalmic artery and siphon connected with bilateral prolonged episodes of amaurosis fugax and transient ischemic attacks. In all three patients the posterior cerebral arteries were major supplying collaterals having high mean velocities of about 100 cm sec(-1) and high velocities in the basilar arteries of 85 cm sec(-1) as well. During follow up no patient had a new stroke, but all experienced orthostatic dizziness and chronic fatigue.

Different cerebral vasoconstrictors have recently been suggested for the treatment of raised intracranial pressure (ICP) in patients with severe traumatic brain lesions. Such treatment may be associated with severe side effects. A porcine model simulating an intracranial mass lesion was utilized to examine the haemodynamic cerebral effects of dihydroergotamine (DHE), a recently introduced pharmacological treatment for raised intracranial pressure. Intracranial hypertension was induced by inflation of two tonometric gastric balloons placed extradurally covering the parieto-occipital region bilaterally. The animals were randomized into one group with six animals receiving 1.0 mg of DHE i.v. followed by a continuous infusion of 0.2 mg/h (high dose) and another group of six animals receiving 0.15 mg i.v. followed by 0.03 mg/h (low dose). Measurements of cerebral blood flow (CBF) and arterio-venous difference in oxygen content (Cavo2) were performed 5, 20, and 60 min after the DHE infusion. Intracranial pressure (ICP), mean arterial blood pressure (MAP) and cerebral electrical activity (EEG) were recorded continuously. In both groups infusion of DHE caused a lasting decrease in ICP probably achieved mainly by a decrease in cerebral blood volume due to constriction of both arterial and venous capacitance vessels. In the group treated with high-dose DHE, but not in that given low-dose DHE, a progressive increase in Cavo2, a fall in jugular venous pH and an increase in EEG delta activity were observed indicating cerebral hypoxia. The study supports the view that DHE may be a valuable tool in the pharmacological treatment of increased ICP in traumatic brain lesions but underscores the importance of a proper dosage.

Cerebral blood flow (CBF) measurements are helpful in managing patients with traumatic brain injury (TBI), and testing the cerebrovascular reactivity to CO(2) provides information about injury severity and outcome. The complexity and potential hazard of performing CBF measurements limits routine clinical use. An alternative approach is to measure the CBF velocity using bedside, non-invasive, and transcranial Doppler (TCD) sonography. This study was performed to investigate if TCD is a useful alternative to CBF in patients with severe TBI.CBF and TCD flow velocity measurements and cerebrovascular reactivity to hypocapnia were simultaneously evaluated in 27 patients with acute TBI. Measurements were performed preoperatively during controlled normocapnia and hypocapnia in patients scheduled for hematoma evacuation under general anesthesia.Although the lack of statistical correlation between the calculated reactivity indices, there was a significant decrease in TCD-mean flow velocity and a decrease in CBF with hypocapnia. CBF and TCD do not seem to be directly interchangeable in determining CO(2)-reactivity in TBI, despite both methods demonstrating deviation in the same direction during hypocapnia. TCD and CBF measurements both provide useful information on cerebrovascular events which, although not interchangeable, may complement each other in clinical scenarios.

Most nuclear medicine clinicians use only visual assessment when interpreting regional cerebral blood flow (rCBF) from single-photon emission computed tomography (SPECT) images in clinical practice. The aims of this study were to develop a new, easy to use, automated method for quantification of rCBF-SPECT and to create normal values by using the method on a normal population. We developed a 3-dimensional method based on a brain-shaped model and the active-shape algorithm. The method defines the surface shape of the brain and then projects the maximum counts 0-1.5 cm deep for designated surface points. These surface projection values are divided into cortical regions representing the different lobes and presented relative to the whole cortex, cerebellum or cerebellar maximum. (99m) Tc-hexa methyl propylene amine oxime (HMPAO) SPECT was performed on 30 healthy volunteers with a mean age of 74 years (range 64-98). The ability of the active-shape algorithm to define the shape of the brain was satisfactory when visually scrutinized. The results of the quantification show rCBF values in the frontal, temporal and parietal lobes of 87-88% using cerebellum as the reference. There were no significant differences in normal rCBF values between male and female subjects and only a weak relation between rCBF and age. In conclusion, our new automated method was able to quantify rCBF-SPECT images and create normal values in ranges as expected. Further studies are needed to assess the clinical value of this method and the normal values.

Background: The preclinical patterns of biological markers for Alzheimer's disease (AD) in vivo need further exploration. The aim of this study was therefore to investigate CSF biomarkers, regional cerebral blood flow (rCBF) and cognitive performance in cognitively healthy older individuals. Method: Within a 2-week period, 32 cognitively healthy older individuals underwent CSF analysis, rCBF measurement and cognitive testing. The CSF was analysed for β-amyloid(1-42) (Aβ42), total tau protein (T-tau) and hyperphosphorylated tau protein (P-tau). The rCBF results were analysed with statistical parametric mapping to investigate rCBF covariance with the other measurements. Results: High CSF P-tau and T-tau levels correlated with decreased rCBF in the right superior posterior medial frontal lobe whereas high CSF P-tau levels also correlated with increased rCBF in the left fronto-temporal border zone area. No significant covariance was seen between rCBF and CSF Aβ42. Neither CSF P-tau and T-tau levels nor rCBF in the current right frontal and left posterior locations were associated with cognitive performance. Conclusions: Our findings suggest a possible correlation between tau pathology and blood flow abnormalities in individuals without any overt cognitive symptoms. An association with AD development is possible but other explanatory mechanisms cannot be excluded.

BACKGROUND: Results from previous studies on the effect of nitrous oxide (N2O) on the cerebral circulation are conflicting. Early reports claim N2O to have no effect whereas recent findings demonstrate a cerebral cortical vasodilatation during N2O inhalation, but the regional cerebral blood flow (CBF) in the subcortical structures is unknown. METHODS: Regional CBF was measured three-dimensionally with single photon emission computer-aided tomography after injection of xenon 133 in 8 spontaneously breathing men (mean age 29.6 yr) during normocapnia and hypocapnia with and without inhalation of 50% N2O. 8 isolated human pial arterial segments were mounted in organ baths. The segments were contracted with prostaglandin F2 alpha and subjected to 30% oxygen and 5.6% carbon dioxide in nitrogen or N2O. RESULTS: Normocapnic young men had a global CBF of 55 +/- 4 ml.100 g-1.min-1. Decreasing end-tidal CO2 tension by 1.3 kPa (9.3 mmHg) reduced CBF uniformly, with a decrease in global CBF to 45 +/- 2 ml.100 g-1.min-1 (P < 0.0001). During normocapnia, inhalation of 50% N2O increased mean CBF to 67 +/- 7 ml.100 g-1.min-1 (P < 0.0001). Inhalation of 50% N2O during hypocapnia increased mean CBF to 63 +/- 5 ml.100 g-1.min-1 (P < 0.0001). During N2O inhalation there was no significant difference in mean CBF between normo- and hypocapnia. However, during hypocapnia, but not during normocapnia, N2O inhalation significantly changed the distribution of regional CBF (P < 0.0001). Compared with hypocapnia without N2O, flow increased through the frontal (143%), parietal (140%) and temporal (133%) regions as well as through insula (151%), basal ganglia (145%) and thalamus (133%). In isolated human pial arteries, addition of N2O changed neither basal tension, nor the contraction elicited by prostaglandin F2 alpha. CONCLUSIONS: Inhalation of 50% N2O increased global CBF mainly by augmenting flow in frontal brain structures. In contrast, changes in carbon dioxide without N2O affected CBF uniformly in the brain. The uneven change in distribution of the CBF when N2O was added during hypocapnia, the reduced carbon dioxide response, and the lack of effect of N2O on isolated human pial arteries suggest that N2O may increase metabolism in selected brain areas. (Less)

Radioactive tracer substances administered to study cerebral functions open a time-dependent window to the brain. We can study e. g. regional cerebral blood flow (rCBF) or chemical properties such as receptors for transmitter substances. Since the tracer substance is carried by the blood flow into the brain its initial distribution will be proportional to the rCBF. The possibility to study more specific brain functions depends on the available time for redistribution of the tracer substance according to its specific chemical affinity. I have studied with the aid of a simple mathem-atic model the time needed for distribution and redistribution of freely diffusable tracer substances in the brain. The results indicate that SPECT measurements of brain receptor properties in theory give at least as good recording conditions as corresponding PET studies. Clinical SPECT receptor studies will presumably soon contribute to our knowledge of the epileptic pathogenic mechanisms.

Seventeen patients with therapy-resistant partial epilepsy were studied in order to compare the localization of the epileptic focus provided by three-dimensional dipole analysis of scalp interictal epilepriform EEG activity to the localization of the ictal pacemaker zone obtained by intracranial recordings. The results were also compared with regional abnormalities in interictal 99m Tc-hexamethylpropy-lenenamine oxime single-photon emission computed tomography (SPECT). Dipole analysis was performed using a well-known commercial computer program based on a three-shell model. For 12 of the 17 patients, the dipoles for all the individual spikes were located in the same area, in two cases, two separate locations were found, and in three cases the dipoles were scattered over a large area. In 8 of the 12 patients with a single dipole location, intracranial ictal recordings revealed a seizure initiation zone corresponding to the dipole location. In another two cases, intraoperative corticography confirmed the dipole findings. In the two remaining patients, the intracranial recordings revealed a different pattern of seizure initiation than had been anticipated from the dipole analysis. In one of the two patients with two dipole locations, intracranial recordings revealed a seizure initiation zone corresponding to one of the two dipole location sites, whereas in the other patient the seizure onset pattern was more complex. In two of the three patients with widely scattered dipole areas, seizure onset was complex, whereas in the third patient a localized seizure onset was found. In 10 of the 12 patients with a single dipole location site, there was good correlation between this site and regions of low flow in the interictal SPECT measurements. In both patients with two dipole areas, there was a low flow area corresponding to at least one of the dipole localizations. In two of the three patients with widespread dipoles, there were major SPECT low-flow areas, whereas in the third patient interictal SPECT was normal. Although our investigations so far are tentative, we think the results indicate that dipole analysis of interictal epileptiform EEG activity may become a useful supplementary method for the localization of the epileptogenic region in patients who are under consideration for surgical therapy, especially if combined with SPECT or other independent localizing techniques.

We present a physiologically stable porcine model designed for sequential assessments of pharmacological effects on mean hemispheric cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) at sustained normocapnia. The dynamic influence of continuously administered fentanyl (0.040 mg.kg-1.h-1 i.v.), nitrous oxide (70%) and pancuronium (0.30 mg.kg-1.h-1 i.v.) on these variables was studied in eight normoventilated pigs. CBF was reliably assessable at 10-min intervals by clearance of intra-arterially injected 133Xe, monitored by an extracranial scintillation detector. CMRO2 was calculated from CBF and the simultaneously measured cerebral arteriovenous difference in blood oxygen content. The intracerebral distribution of a contrast medium injected into the external and internal carotid arteries was studied by angiography, and the cerebral venous outflow was investigated by measurements of the distribution of an intra-arterially administered non-diffusible tracer, [99mTc]pertechnetate, to the internal and external jugular veins. After a 3-h equilibration period, CBF and CMRO2 were determined on six occasions over a study period lasting 1 h 40 min. The mean ranges of these variables were 56-60 and 1.9-2.0 ml.100 g-1.min-1, respectively. We conclude that the model enables repeated assessments of CBF and CMRO2 under stable physiological background conditions and thus valid cerebral pharmacodynamic investigations of drugs given for anaesthesia.

The effect of moderate hypoglycemia (p-glucose, 2.0 +/- 0.3 mmol/L; mean +/- SD) on regional cerebral blood flow (rCBF) was studied in a group of 10 healthy, right-handed men (aged 23 to 28 years) using an intravenous xenon 133 single photon emission computed tomography technique (SPECT). After 10 minutes of hypoglycemia, global CBF had increased to 46.3 +/- 9.6 mL/100 g/min compared with the initial normoglycemic flow of 38.6 +/- 6.8 mL/100 g/min (P less than .01). The relative distribution of the rCBF changed significantly (P less than .05, ANOVA) from before to during hypoglycemia. Of the 10 regions analyzed, the highest increments in rCBF during hypoglycemia were found in the frontal (21.5% +/- 15.2%) and parietal (20.6% +/- 14.2%) lobes, and the lowest (10.7% +/- 9.4%) were found in the pons/brainstem regions. The increase in rCBF persisted for 15 minutes after normalization of blood glucose. The persisting high flow after hypoglycemia affected all regions, but a further 10.1% +/- 7.2% increase was observed in the pons/brainstem area (P less than .05). The CBF was significantly higher in the right compared with the left hemisphere (2.8%, 1.2%, and 3.9%, respectively; P less than .05) in all measurements. A decrease in brain volume was found at the final examination, compared with the hypoglycemic state (2.6%; P less than .05). It is concluded that moderate hypoglycemia leads to a marked increase in CBF and in the relative distribution of rCBF, which persists in the immediate period after normalization of the blood glucose level.

Cerebral blood flow (CBF) and the cerebral vasoreactivity was measured in patients with cerebrovascular disease and longstanding occlusion of the common carotid artery (CCA). In addition, regional CBF was correlated with transcranial doppler (TCD) measurements at baseline and during 6% CO2 inhalation and after intravenous administration of 1 g of acetazolamide. Twelve patients with a mean age of 62 years (range 45 to 71 years) were included, and the data compared to age-matched healthy controls. CBF was measured by intravenous injection of xenon-133 and SPECT (Tomomatic 564). TCD of the middle cerebral artery (MCA) was done by EME TC-64B. A very low global CBF value of 28 +/- 5 (SD) ml 100 g-1 min-1 was found at baseline as compared to 55 +/- 5 ml 100 g-1 min-1 in the normal controls. During 6% CO2-inhalation and after acetazolamide administration, CBF increased by 58 +/- 24% and 51 +/- 21%, respectively, indicating substantial collateral supply. Correlative analysis of CBF in the MCA territory and TCD in the MCA showed statistical significance only for the pooled data, i.e. compiling the data obtained during baseline and the two vasodilatory tests, and then only for the mean and peak TCD velocity (e.g. r = 0.59, p less than 0.002, n = 35, mean velocity, right side). We conclude that TCD measurements do not predict regional CBF in patients with CCA occlusion. The study emphasizes that these two methods yield supplementary information, with TCD measurements providing information of the circle of Willis and CBF studies of the flow distribution.