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Biomedical subjects

A R Andersen

Publications and source records attributed to A R Andersen.

At least 19 recordsLinked to original sources

[Psychosocial consequences and surgical treatment of epilepsy. A review].

Epilepsy is one the commonest neurological diseases. In 25% of the cases, particularly in patients with temporal foci, the seizures prove to be resistant to medicinal treatment. Several investigations have stressed that these patients have pronounced psychosocial problems which may be more important to the patient than the actual seizures. Taking into consideration the WHO definition of health as complete physical, mental and social well-being, patients with epilepsy have problems in all of these dimensions. The major problems are social isolation and employment. Surgical treatment of epilepsy has a pronounced effect on the seizures in 90% of the operations in the best series but it is still uncertain whether reduction in the number of seizures also implies better quality of life. The present data suggest improvement in the psychosocial conditions of the patients who functioned best preoperatively and who became seizure-free after operation. The importance of further longitudinal studies emphasizing the psychosocial aspects is stressed.

Epilepsy

Reduced regional cerebral blood flow in Huntington's disease studied by SPECT.

Regional cerebral blood flow (rCBF) was studied in 18 patients with Huntington's disease (HD) and 19 age- and sex-matched controls with high resolution single photon emission computerised tomography (SPECT), using Tc-99m-HMPAO. Significant reductions in tracer uptake were found in the caudate and lentiform nuclei (20 and 8%) and in the cerebral cortex, especially in the frontal and parietal areas (11-13%). No significant reductions were found in the thalamus, mesial temporal cortex, and occipital cortex. Fourteen patients had neuropsychological testing. Relationship between rCBF and cognitive function was tested by regression analysis. A linear relationship was found between test scores of Wisconsin Card Sorting Test, Picture Arrangement Test and blood flow in the caudate nucleus. Other tests of cognitive function (Block Design Test, Face and Word Recognition Test, Street Fragmented Pictures Test, and Similarities Test) correlated better with flow in the cortical regions believed to be involved in solving those particular tests. These findings indicate, that blood flow is reduced in both cortical and subcortical structures in symptomatic HD, and that both reductions in cortical and subcortical blood flow may be related to cognitive function in HD.

Adult

[Surgical treatment of epilepsy resistant to drug therapy. A review].

The prevalence of epilepsy is 7-9 cases per 1,000 population, corresponding to 440,000 individuals in Denmark. Approximately 1/4 of these individuals have seizures refractory to anticonvulsant medications and most of them have an epileptic focus in the temporal lobe. Epilepsy refractory to anticonvulsant medication is an incapacitating disease with high costs for the person and the society. The main problems are polypharmacy with side effects, suspicion of neurodegenerative consequences and a higher mortality. The modern era of epilepsy surgery began more than 100 years ago and since then, the developments in neurophysiology and neuroimaging have made it possible to demonstrate the epileptic focus with relatively high precision. As a consequence of this, the volume of the resected tissue has diminished and the operative complications become less frequent. The somatic and neuropsychological effects of a cortical resection are discrete and compensated by a general improvement in performance. Surgical treatment of epilepsy should no longer be considered as a last resort, but as a realistic treatment in cases of medication failure.

Anticonvulsants

[3-year experiences with surgical treatment of epilepsy at the Hvidovre hospital].

The results of a retrospective survey of 48 patients submitted to neurosurgery for medically intractable epilepsy are presented. Twenty-eight patients were treated with selective amygdalohippocampectomy, one with temporal lobe resection, 12 with anterior callosotomy and seven with a total callosotomy. Of the amygdalohippocampectomized patients and the one with temporal lobe resection (n = 29), 52% were seizure free, 17% experienced rare seizures, 7% had a worthwhile improvement while 24% observed no worthwhile improvement (follow-up time 6 to 36 months). Of the callosotomized patients, 11% were free from generalized seizures, 69% had a significant seizure reduction and 18% experienced no worthwhile improvement. The observed neurological complications were: one patient had hemianopia, one had superior quadrant anopia, four developed unilateral anosmia and one complete anosmia. The callosotomized patients, with two exceptions, were all mentally and physically handicapped. In the callosotomy group, two patients died, one from a intracerebral hematoma three months after the operation and another patient seven months postoperatively from unknown causes.

Adult

99mTc-d,l-HMPAO and SPECT of the brain in normal aging.

Single photon emission computed tomography (SPECT) with 99mTc-d,l-hexamethylpropyleneamine oxime (99mTc-d,l-HMPAO) was used to determine global and regional CBF in 53 healthy subjects aged 21-83 years. For the whole group, global CBF normalized to the cerebellum was 86.4% +/- 8.4 (SD). The contribution of age, sex, and atrophy to variations in global CBF was studied using stepwise multiple regression analysis. There was a significant negative correlation of global CBF with subjective ratings of cortical atrophy, but not with ratings of ventricular size, Evans ratio, sex, or age. In a subgroup of 33 subjects, in whom volumetric measurements of atrophy were performed, cortical atrophy was the only significant determinant for global CBF, accounting for 27% of its variance. Mean global CBF as measured with the 133Xe inhalation technique and SPECT was 54 +/- 9 ml/100 g/min and did not correlate significantly with age. There was a preferential decline of CBF in the frontal cortex with advancing age. The side-to-side asymmetry of several regions of interest increased with age. A method was described for estimation of subcortical CBF, which decreased with advancing cortical atrophy. The relative area of the subcortical low-flow region increased with age. These results are useful in distinguishing the effects of age and simple atrophy from disease effects, when the 99mTc-d,l-HMPAO method is used.

Adult

Timing and topography of cerebral blood flow, aura, and headache during migraine attacks.

Ten years of study has resulted in considerable but fragmented knowledge about regional cerebral blood flow in migraine with aura (classic migraine). In the present study, the number of repeatedly studied patients (n = 63) was large enough to determine statistically significant sequences of events and statistically significant spatial relations. The first observable event was a decrease of regional cerebral blood flow posteriorly in one cerebral hemisphere. Further development of this pathological process was accompanied by the aura symptoms. Thereafter headache occurred while regional cerebral blood flow remained decreased. During the headache phase, regional cerebral blood flow gradually changed from abnormally low to abnormally high without apparent change in headache. In some patients headache disappeared while regional cerebral blood flow remained increased. Although regional cerebral blood flow reduction and aura symptoms in the great majority of patients were unilateral, one-third had bilateral headache. Unilateral headache usually localized to the side on which regional cerebral blood flow was reduced and from which the aura symptoms originated (i.e., aura symptoms were perceived to occur contralaterally but presumably originated in the hypoperfused hemisphere). Our results suggest a simple model for migraine attacks: A pathological disturbance in one cerebral hemisphere causes the aura symptoms and after a time delay, it also causes the headache by stimulating local vascular nociceptors. Bilateral headache caused by a unilateral cerebral disturbance may be explained by recent neuroanatomical and neurophysiological findings.

Adolescent

SPECT in the presurgical evaluation of patients with temporal lobe epilepsy--a preliminary report.

Twenty-eight patients with drug resistant temporal lobe epilepsy (DRTLE) were studied using single photon emission computed tomography (SPECT) using xenon-133 inhalation and Tc99m-d, 1-HMPAO with TOMOMATIC 64 as part of a presurgical evaluation programme. The visually evaluated flow-images were studied after blinding and the results subsequently compared to the EEG, MRI and CT scanning studies. In 24 patients a significant low flow region was seen in one temporal lobe. The SPECT result corresponded to the EEG findings in all but 6 patients. In 2 of these patients no side localization was indicated by EEG, while in four patients the EEG suggested that the opposite side was epileptogenic. Ictal SPECT and MRI/CT agreed with the resting SPECT study in three patients, while one patient has remained undiagnosed with respect to side-localization. In 14 patients discordance between SPECT and the CT scan was observed, but in 11 of these patients the SPECT study correlated with the other focal diagnostic tools. In 11 of the 21 patients studied by MRI, the results corresponded to SPECT; in 7 of the 10 which did not correspond, ictal studies of EEG and SPECT defined the side, in four of these 7 patients. Using the neuroimaging tools in concert 16 patients have been selected for surgery. All patients have benefited from surgery. These preliminary results correspond favourably with earlier studies comparing SPECT and PET with CT, MR and EEG.

Adult

Angiotensin converting enzyme inhibition, CBF autoregulation, and ICP in patients with normal-pressure hydrocephalus.

Fourteen patients with normal pressure hydrocephalus had the autoregulation of cerebral blood flow (CBF) and intracranial pressure (ICP) investigated. In 8 of the patients the effect of Captopril on ICP and CBF was also investigated. The mean arterial blood pressure (MABP) was 109 mmHg (intra-arterially), and ICP was 11 mmHg (intraventricularly). Changes in global CBF were estimated by the arterio-venous oxygen difference method. The autoregulation of CBF was present in 13 of the patients (p less than 0.01). The lower limit of CBF autoregulation was 86% of the baseline perfusion pressure. One hour after 50 mg of captopril perorally, MABP was reduced 16 mmHg, and ICP and CBF were unchanged. The autoregulation was maintained and the lower limit was decreased 19 mmHg. Thus patients would be expected to benefit from captopril treatment in hypotensive anaesthesia.

Administration, Oral

The effect of fosinopril sodium on cerebral blood flow in moderate essential hypertension.

The effect of the angiotensin converting enzyme (ACE) inhibitor fosinopril sodium on regional cerebral blood flow (rCBF) was investigated in 8 patients with moderate essential hypertension. A constant dose of chlorthalidone (25 mg/day) was given to stimulate the renin angiotensin system, and fosinopril sodium was given in incremental doses (10 to 40 mg/day) with the aim of obtaining a diastolic blood pressure at or below 90 mm Hg. Regional CBF was measured with xenon-133 inhalation tomography. Repetitive measurements were made at the start of treatment and again after 4 to 12 weeks treatment in the resting supine position, and during lower body negative pressure (LBNP) as a substitute for the upright position. Four hours after the first 10 mg dose of fosinopril the mean arterial pressure (MAP) had been reduced from 127 +/- 13 mm Hg to 105 +/- 9 mm Hg (P less than .01) without any significant change in mean CBF (55 +/- 9 mL/(100 g X min) at baseline versus 52 +/- 9 mL/(100 g X min) after fosinopril). After prolonged treatment with chlorthalidone and fosinopril, mean CBF was still unchanged from baseline levels, when measured 4 and 24 h after a single dose of fosinopril, despite a 10% reduction in MAP (P less than .01). LBNP did not lead to any significant change in rCBF. The regional distribution of CBF was normal in all patients throughout the study. We conclude that treatment with fosinopril sodium causes a moderate fall in blood pressure without any adverse effects on rCBF.

Adult

Cerebral blood flow in progressive aphasia without dementia. Case report, using 133xenon inhalation, technetium 99m hexamethylpropyleneamine oxime and single photon emission computerized tomography.

We report a case of progressive aphasia without clinical signs of intellectual or behavioral impairment, satisfying Mesulam's clinical criteria of primary progressive aphasia, as 4 yrs of extensive psychometric testing and radiological imaging, comprising CT and MRI, failed to detect evidence of relevant involvement outside the left perisylvian regions. Cranial CT was normal but MRI showed multiple bilateral lesions in the deep white matter. Cerebral blood flow (CBF) studies by single photon emission computerized tomography, however, showed an initial frontotemporal focus of hypoperfusion that progressively extended to include most of the ipsilateral hemisphere and the contralateral frontal lobe. This suggests that CBF imaging may yet be the most sensitive technique in revealing subclinical injury in the degenerative brain diseases of focal onset.

Administration, Inhalation

Computerized analysis of cerebral blood flow autoregulation in humans: validation of a method for pharmacologic studies.

Cerebral blood flow (CBF) autoregulation in the supine position without tilting using systemic ganglion-blockade (trimetaphane camphosulfonas) combined with lower body vacuum is evaluated. Automatic computerized curve-fitting analysis for assessment of the lower limit (LL) of autoregulation is introduced. Global CBF was evaluated using the arteriovenous-O2-difference method in 12 volunteers and in seven patients with chronic arterial hypertension. Classic autoregulatory curves were found in all cases. The LL of CBF autoregulation was 85 +/- 5 mm Hg in the volunteers and 113 +/- 7 mm Hg in the hypertensive patients. In seven of the volunteers, the autoregulatory study was performed twice in 1 day; a small but significant shift of LL toward higher blood pressure (BP) values was observed in the second test (3 mm Hg). In five of the hypertensive patients, regional CBF (rCBF) was measured by single-photon emission computed tomography (SPECT) of inhaled xenon-133. The median global CBF decreased from 62 to 45 ml/100 g/min during the mean arterial BP (MABP) decrease from 110 to 68 mm Hg. The regional distribution of CBF was normal at baseline as well as during hypotension. The method is suitable for pharmacologic studies of cerebral autoregulation.

Adult

The effect of the benzodiazepine antagonist flumazenil on regional cerebral blood flow in human volunteers.

The influence of the benzodiazepine antagonist flumazenil on regional cerebral blood flow (rCBF) was investigated in ten healthy, alert volunteers. The design was a randomized, placebo-controlled, double-blind, cross-over study. rCBF was measured by 133-Xe inhalation and single photon emission computerized tomography, SPECT, immediately before, and 5 and 35 min after intravenous injection of flumazenil 1.0 mg or placebo. In addition, mean arterial blood pressures or PaCO2, rCBF were analysed for changes in various regions of interest (RoI). No alterations were found either in the global CBF or in rCBF in RoI after flumazenil injection. The results showed that a clinically active dose of flumazenil did not directly affect the cerebral circulation in the normal brain and indicated absence of significant intrinsic activity of the drug.

Adult

Angiotensin-converting enzyme inhibition and regional cerebral blood flow in acute stroke.

The effect of the angiotensin-converting enzyme (ACE) inhibitor captopril on regional cerebral blood flow (rCBF) was studied in 12 patients within 5 days after their first acute stroke. rCBF was studied by xenon-133 inhalation and single-photon emission computed tomography (SPECT) scan before and 1 h after oral administration of 25 mg captopril. No increase in rCBF was observed in any of the 12 patients included in the study. In only one patient was there a slight redistribution of blood flow in favor of the low-flow area, but the absolute flow value did not increase. Captopril did not cause any significant change in mean hemispheric blood flow, mean arterial blood pressure (MAP), or end-expiratory CO2 fraction (FECO2). The assumption that ACE inhibition might increase cerebral blood flow in the periinfarct zone and preserve some still viable brain tissue could not be verified in the present study.

Acute Disease

Angiotensin converting enzyme inhibition and cerebral blood flow autoregulation in normotensive and hypertensive man.

The acute effect on the lower limit of cerebral blood flow (CBF) autoregulation of an angiotensin converting enzyme (ACE) inhibitor, captopril, was studied in normotensive volunteers and in hypertensive patients. Baseline CBF was measured using xenon-133 inhalation tomography, and changes in CBF were measured using the arterio-venous oxygen difference method. Cerebral blood flow autoregulation was studied in two separate normotensive groups, one group of 12 volunteers serving as a control, and one group of 12 volunteers studied after the administration of captopril 50 mg. In a group of seven hypertensive patients CBF autoregulation was studied before and 1 h after the administration of captopril 25 mg. In the normotensive volunteers the median lower limit of CBF autoregulation was 83 and 74 mmHg in the untreated and the captopril-treated group, respectively, with no significant difference between the two groups. In five of the hypertensive patients the lower limit of CBF autoregulation was lowered by captopril, in median by 22 mmHg. However, in two patients it was increased, by 3 and 13 mmHg, respectively. It is proposed that the shift in the lower limit of CBF autoregulation seen in some of our cases, and which has previously been documented in experimental studies, may be dependent on the activity of the sympathetic nervous system.

Adult

99mTc-D,L-hexamethylene-propyleneamine oxime (99mTc-HMPAO): basic kinetic studies of a tracer of cerebral blood flow.

The lipophilic 99mTc-D,L-hexamethylene-propyleneamine oxime (99mTc-HMPAO) has been developed for regional cerebral blood flow (rCBF) measurements by single photon emission computed tomography (SPECT). The molecule is unstable and converts rapidly from the lipophilic form, which passes the blood-brain barrier (BBB), to the hydrophilic form, which is unable to pass the BBB and is trapped in the brain. The rate-limiting step for this conversion is probably dependent on the reductant gluthathione. The lipophilic input to the brain can be estimated by rapid octanol extraction of lipophilic tracer from arterial blood. The input takes place during the first few minutes after tracer injection. The first-pass extraction from blood to brain E is high (0.72 at a CBF of 0.59 ml/g/min) in human studies as measured by the indicator dilution method. It is dependent on the CBF level and decreases when CBF increases. It is also dependent on binding to proteins and blood constituents. 99mTc-HMPAO is initially distributed like rCBF. In measuring the retention in the human brain after intravenous and intracarotid injection of 99mTc-HMPAO, an early back-diffusion (brain to blood) is seen. This lasts only 2-3 min. The back-diffusion is flow dependent, leading to a preferential loss of activity from the high flow regions of the brain. This can be corrected for by an algorithm. The effect of the algorithm is that the steady-state 99mTc-HMPAO distribution images obtained from 10 min to 2-3 h after injection of tracer agrees more closely with rCBF images as measured by reference CBF methods using SPECT and positron emission tomography (human studies) and quantitated autoradiography (rats). The retention in the brain is very stable when the early back-diffusion has ceased, and only a small loss of tracer amounting to 0.4%/h is observed in most human cases during the next 24 h. This review concludes that 99mTc-HMPAO is suitable for measurements of rCBF by SPECT. A few examples of clinical application are given.

Cerebrovascular Circulation

Delayed hyperemia following hypoperfusion in classic migraine. Single photon emission computed tomographic demonstration.

Regional cerebral blood flow (rCBF) was measured in seven patients during classic migraine attacks. Single photon emission computed tomography was performed soon after hospital admission, and three to eight hours, 20 to 24 hours, and one week later after the onset of symptoms. Initially reduced rCBF persisting up to three hours was observed in the hemisphere appropriate to the focal neurologic deficit; hyperperfusion was noted later in the same region in these patients. At 24 hours rCBF was normal in four patients, hyperemia persisted in two patients, and one patient was not restudied. The area of interest demonstrated a mean decrease of 19% +/- 7% in side-to-side asymmetry when compared with the contralateral region. In three to eight hours this reversed to a mean increase of 19% +/- 4% (delayed hyperemia). No asymmetries were observed after one week. The late hyperemic asymmetry often persisted beyond the duration of the clinical headache. It is postulated that this tardive regional hyperperfusion is a consequence of previous focal arteriolar vasoconstriction. This vascular sequence of events further delineates the diagnostic merit of studying rCBF by noninvasive single photon emission computed tomography in migraine.

Adult

The retention mechanism of technetium-99m-HM-PAO: intracellular reaction with glutathione.

Preparations of d,l- and meso-hexamethylpropyleneamine oxime (HM-PAO) labeled with technetium-99m were added to rat brain homogenates diluted with phosphate buffer (1:10). The conversion of d,l-HM-PAO to hydrophilic forms took place with an initial rate constant of 0.12 min-1. Incubation of the brain homogenate with 2% diethyl maleate for 5 h decreased the homogenate's measured glutathione (GSH) concentration from 160 to 16 microM and decreased the conversion rate to 0.012 min-1. Buffered aqueous solutions of glutathione rapidly converted the HM-PAO tracers to hydrophilic forms having the same chromatographic characteristics as found in the brain homogenates. The rate constant for the conversion reaction of d,l-HM-PAO in GSH aqueous solution was 208 and 317 L/mol/min in two different assay systems and for meso-HM-PAO the values were 14.7 and 23.2 L/mol/min, respectively. Rat brain has a GSH concentration of about 2.3 mM and the conversion of the d,l-HM-PAO due to GSH alone should proceed with a rate constant of 0.48 to 0.73 min-1 and be correspondingly 14-fold slower for meso-HM-PAO. In human brain, the in vivo data of Lassen et al. show a conversion rate constant of 0.80 min-1. This correspondence of values supports the notion that GSH may be important for the in vivo conversion of 99mTc-labeled HM-PAO to hydrophilic forms and may be the mechanism of trapping in brain and other cells. A kinetic model for the trapping of d,l- and meso-HM-PAO in tissue is developed that is based on data of GSH concentration in various organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals