Karl-Fredrik Lindegaard

Cerebral autoregulation dynamics in humans.

We studied the response of cerebral blood flow to acute step decreases in arterial blood pressure noninvasively and nonpharmacologically in 10 normal volunteers during normocapnia, hypocapnia, and hypercapnia. The step (approximately 20 mm Hg) was induced by rapidly deflating thigh blood pressure cuffs following a 2-minute inflation above systolic blood pressure. Instantaneous arterial blood pressure was measured by a new servo-cuff method, and cerebral blood flow changes were assessed by transcranial Doppler recording of middle cerebral artery blood flow velocity. In hypocapnia, full restoration of blood flow to the pretest level was seen as early as 4.1 seconds after the step decrease in blood pressure, while the response was slower in normocapnia and hypercapnia. The time course of cerebrovascular resistance was calculated from blood pressure and blood flow recordings, and rate of regulation was determined as the normalized change in cerebrovascular resistance per second during 2.5 seconds just after the step decrease in blood pressure. The reference for normalization was the calculated change in cerebrovascular resistance that would have nullified the effects of the step decrease in arterial blood pressure on cerebral blood flow. The rate of regulation was 0.38, 0.20, and 0.11/sec in hypocapnia, normocapnia, and hypercapnia, respectively. There was a highly significant inverse relation between rate of regulation and PaCO2 (p less than 0.001), indicating that the response rate of cerebral autoregulation in awake normal humans is profoundly dependent on vascular tone.

Assessment of cerebral autoregulation dynamics from simultaneous arterial and venous transcranial Doppler recordings in humans.

We investigated the validity of transcranial Doppler recordings for the analysis of dynamic responses of cerebral autoregulation. We found no significant differences in percentage changes among maximal (centerline) blood flow velocity, cross-sectional mean blood flow velocity, and signal power-estimated blood flow during 24-mm Hg stepwise changes in arterial blood pressure. We investigated blood flow propagation delays in the cerebral circulation with simultaneous Doppler recordings from the middle cerebral artery and the straight sinus. The time for a stepwise decrease in blood flow to propagate through the cerebral circulation was only 200 msec. Brief (1.37-second) carotid artery compression tests also demonstrated that the volume compliance effects of the cerebral vascular bed were small, only about 2.2% of normal blood flow in 1 second. Furthermore, transients associated with inertial and volume compliance died out after 108 msec. We also investigated the hypothesis that autoregulatory responses are influenced by hyperventilation using the same brief carotid artery compressions. One second after release, the flow index increased by 17% during normocapnia and 36% during hypocapnia. After 5 seconds, the flow index demonstrated a clear oscillatory response during hypocapnia that was not seen during normocapnia. These results suggest that the intact human cerebral circulation in the absence of pharmacological influences does not function as predicted from pial vessel observations in animals.

Cerebral Vasospasm After Subarachnoid Haemorrhage Investigated by Means of Transcranial Doppler Ultrasound

Measurements of flow velocity in defined segments of the basal cerebral arteries can be obtained through the intact adult skull using 2 MHz pulsed Doppler ultrasound. We compared flow velocity in these vessels with findings from 56 cerebral angiographies obtained in 51 patients at from day 1 to day 21 after subarachnoid haemorrhage (SAH). The diameter of the proximal segment of the middle cerebral, anterior cerebral, and posterior cerebral arteries (MCA, ACA, and PCA, respectively) were measured from anteroposterior films produced in one angiographic laboratory. In patients investigated on day 1-2, the median MCA diameter was 2.8 mm with range 2.3-3.4 mm. The median flow velocity was 56 cm/s, range 36-88 cm/s (within normal limits). There was a clear inverse relationship between the MCA diameter and MCA flow velocity. Eleven of the 13 MCAs having diameter 1.5 mm or less showed flow velocity in excess of 140 cm/s. This seems a useful limit to diagnose pronounced MCA spasm (50% diameter reduction) with this method. Further clues to the severity of MCA spasm were obtained from the ratio calculated dividing the MCA flow velocity by the flow velocity in the ipsilateral, extracranial internal carotid artery (ICA), since spasm probably does not involve the neck vessels. This ratio was from 1.1 to 2.3, median 1.7 at day 1-2, but rose to over 10 in patients with the most severe MCA lumen narrowing. The PCA flow velocity was inversely related to the PCA diameter. Assessment of ACA spasm requires considering findings from both hemispheres combined, since the two proximal ACAs usually anastomose through the anterior communicating artery.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of transcranial Doppler and cerebral blood flow studies to assess cerebral vasoreactivity.

Background and Purpose The aim of this study was to determine the ability of transcranial Doppler ultrasonography when used to assess cerebral vasoreactivity. The results of this method were compared with regional cerebral blood flow measurements. Methods Forty-three patients with symptoms suggesting cerebrovascular disease took part Transcranial Doppler findings in the middle cerebral arteries were compared with regional cerebral blood flow in the corresponding perfusion territories before and after acetazolamide administration. Results There was a significant positive correlation between the absolute increase in cerebral blood flow in milliliters per 100 g per minute and the percent increase in velocity (r=0.63). The right-left, side-to-side difference of the acetazolamide response obtained by the two methods also showed a positive correlation (r=0.80). Control limits obtained from healthy subjects were used for both the blood flow increase (absolute values and asymmetry in absolute values) and the velocity increase (percent increase and asymmetry in percent increase). The two methods then agreed in their evaluation of vasoreactivity in 74 (86%) of the 86 middle cerebral artery perfusion territories; 20 (23%) were assessed by both methods as having a reduced vasodilatory reserve. Eleven hemispheres with a slightly reduced regional cerebral blood flow response to acetazolamide were not detected by transcranial Doppler, whereas all territories with a marked reduction were identified by Doppler. Only one hemisphere with a normal cerebral blood flow increase after acetazolamide administration was assessed by Doppler as having reduced vasoreactivity. Conclusions Transcranial Doppler and the acetazolamide test may be used in clinical situations to assess cerebral vasoreactivity.

Oligodendroglioma. Histologic Evaluation and Prognosis

Abstract All oligodendrogliomas registered in Norway during a 25-year period (1953–1977) were studied to establish the frequency of different histologic features and to compare them with survival data of the patients. The minimum observation time was five years. The original tumor specimens from 208 patients were independently reexamined by two pathologists. The characteristic Oligodendroglioma of this series was of medium cell density (53% of lesions), with moderate nuclear atypia, with vascular endothelial proliferation (53%), calcification (56%), with from one to five mitotic figures per ten high power fields, and without microcystic degenerative changes (58%). Subpial tumor cell infiltration, perivascular lymphocytic infiltration and local leptomeningeal invasion were present in a minority of cases. In 11 cases autopsy material was the only source of diagnosis. Microcysts, necrosis, and cell density were the only histologic features of prognostic significance. Subpial infiltrative growth was of suggestive prognostic value. There was no significant association between the number of mitotic figures and survival. Vascular endothelial proliferation, calcification, pronounced nuclear atypia, perivascular lymphocytic infiltration and local leptomeningeal invasion were of no significant prognostic value. Age at operation did not alter these conclusions, neither did sex nor duration of preoperative symptoms.

Effect of acetazolamide on cerebral artery blood velocity and regional cerebral blood flow in normal subjects.

SummaryThe effect of intravenous acetazolamide L g on cerebral artery blood velocity and regional blood flow (rCBF) was investigated in eight normal subjects. Blood velocity was measured with 2 MHz pulsed Doppler in the proximal segments of the middle, anterior and posterior cerebral artery (MCA, ACA, and PCA) and in the distal extracranial internal carotid artery (ICA). The rCBF in the regions of interest tentatively corresponding to the perfusion territories of these vessels was estimated using133Xe inhalation and a rapidly rotating single photon emission computer tomograph.Both blood velocity and rCBF increased after acetazolamide. There was no significant difference between the percentage ICA blood velocity increase (22 ± 12%) and the percentage rCBF increase in the ICA region of interest (25 ± 9%). In the MCA, ACA, and PCA, however, blood velocity increased more (mean increase 36–42%) than the rCBF in the corresponding regions of interest (mean increase 24–26%). These differences were highly significant suggesting a direct and site specific effect of acetazolamide in narrowing the lumen of the proximal MCA, ACA, and PCA, but not of the extracranial ICA. We also propose that the effect of acetazolamide induces reciprocal changes in the extent of adjacent perfusion territories in individual brain hemispheres.Data compiled from all subjects investigated at two very different perfusion levels (before and after acetazolamide) revealed a significant positive correlation between blood velocity and rCBF.

Blood velocity and regional blood flow in defined cerebral artery systems

SummaryCerebral artery blood velocity and regional blood flow (rCBF) were investigated in 17 normal subjects. Blood velocity was measured with 2 MHz pulsed Doppler ultrasound in the proximal segments of the middle, anterior and posterior cerebral artery (MCA, ACA, and PCA) and in the distal extracranial internal carotid artery (ICA). The rCBF in the regions of interest tentatively corresponding to the perfusion territories of these vessels was estimated using133Xe inhalation and a rapidly rotating single photon emission computer tomograph.Concomitant capnograph recordings showed that the end-expiratory pCO2 was higher during the rCBF than during the blood velocity examinations. This difference was highly significant. While there was no significant correlation between blood velocity and rCBF when these clear differences in pCO2 were disregarded, we did find significant positive correlations when the data were normalized to a standard pCO2 (5.3 kPa) using accepted formulas. The best correlation was found for the MCA (r=0.630, p<0.001) and the PCA (r=0.73, p < 0.001), with a lower correlation in the ACA (r=0.49, p<0.01) and the ICA (r=0.41, p<0.05). The estimated blood velocity (V) given rCBF=0 was not significantly different from 0.The results support the validity of expressing the relationship between blood velocity (V) and rCBF in defined cerebral artery systems as: V=1/60(rCBF) T (A)−1, where A represents the area of the lumen of the vessel segment where the velocity is being measured, and T denotes the size of the brain region being perfused from this artery.

Cerebral perfusion during nonpulsatile cardiopulmonary bypass

The recording of middle cerebral artery (MCA) flow velocity by the transcranial Doppler method offers a new, noninvasive, continuous technique for studies of cerebral circulation. Comparative studies of electromagnetic internal carotid artery (ICA) flowmetry and MCA flow velocity by the transcranial Doppler technique have demonstrated that observed changes in MCA flow velocities reflect concomitant changes in cerebral circulation. Eleven high-risk patients undergoing cardiopulmonary bypass (CPB) procedures were included in a pilot study. Arterial blood pressure (BP), central venous pressure, and epidural intracranial pressure (EDP) were recorded during CPB. Cerebral electrical activity was recorded by a cerebral function monitor. Flow velocity in the MCA was increased during nonpulsatile CPB in 10 of the 11 patients. This increase was related to the degree of hemodilution, and the flow velocity during steady-state CPB was 80 to 300% of the prebypass value. The MCA flow velocity changed, however, in a pressure-passive manner with the cerebral perfusion pressure (CPP = BP - EDP) in the individual patient, which indicates that cerebral autoregulation was not operative. During the first 15 minutes after termination of bypass, the MCA flow velocity was reduced, but remained higher than the prebypass level, 110 to 210% of the level during the last 5 minutes preceding CPB.

Dissociation between cerebral autoregulation and carbon dioxide reactivity during nonpulsatile cardiopulmonary bypass

Five patients undergoing cardiopulmonary bypass (CPB) procedures were extensively monitored because of anticipated high risk for neurological complications. Arterial blood pressure (BP), central venous pressure, and epidural intracranial pressure (EDP) were continuously recorded throughout CPB; thus, information on the cerebral perfusion pressure (CPP) was also continuously available (CPP = BP - EDP). Cerebral electrical activity was recorded by a cerebral function monitor. The flow velocity in the middle cerebral artery (MCA) was recorded using a transcranial Doppler technique. During steady-state CPB (constant hematocrit, constant temperature, and constant flow from the heart-lung machine) partial pressure of arterial carbon dioxide (PaCO2) was repeatedly changed to study the effect of changes in this variable on MCA flow velocity during nonpulsatile bypass. During CPB with constant temperature, hematocrit, and PaCO2, the effect of changes in CPP on MCA flow velocity was recorded and analyzed. During nonpulsatile, moderately hypothermic (28 degrees to 32 degrees C), low-flow (1.5 L/min/m2) CPB, there was no evidence of cerebral autoregulation, with CPP levels ranging from 20 to 60 mm Hg. The CO2 reactivity, however, was clearly present and in the range of 1.9 to 4.1%/mm Hg, indicating that there was a dissociation between cerebral autoregulation and CO2 reactivity under these circumstances.

Cognitive outcome after aneurysmal subarachnoid hemorrhage : Time course of recovery and relationship to clinical, radiological, and management parameters

OBJECTIVEAlthough many patients show a satisfactory physical outcome after aneurysmal subarachnoid hemorrhage (SAH), disabling cognitive dysfunction may still be present. This study focuses on the time course of cognitive recovery during the first year after aneurysmal SAH, and relates the neuropsychological test results to clinical, radiological, and management parameters. METHODSThirty-two patients were followed prospectively with neuropsychological examinations at 3, 6, and 12 months after SAH. Test results were compared with clinical entry variables, management variables, and pre- and postoperative radiological findings. RESULTSThe time course of cognitive recovery after aneurysmal SAH is heterogeneous, with motor and psychomotor functions recovering within the first 6 months, whereas verbal memory did not improve significantly until at least 6 months after the ictus. Clinical and radiological parameters reflecting the impact of the bleed were related to memory function, intelligence, and aphasia. The site of aneurysm and mode of treatment could not be linked to neuropsychological outcome. The time length of volume-controlled mechanical ventilation as a reflector of the aggregated consequences of being subjected to an aneurysm rupture correlated with both motor and psychomotor functioning and memory performance, predominantly 6 to 12 months after SAH, but was not linked to intelligence or aphasia. CONCLUSIONThe various cognitive functions have different time courses of recovery, with verbal memory requiring the longest time. Parameters reflecting the impact of the bleed and patient management can be linked to neuropsychological outcome.