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Biomedical subjects

S Asenbaum

Publications and source records attributed to S Asenbaum.

At least 55 records · Page 3Linked to original sources
PubMed1997

[Sleep disorders in neurology. Hypersomnia].

Hypersomnia (excessive sleepiness) accompanies many diseases. 14% of the total Austrian population regularly have problems staying awake during the day or are prone to taking spontaneous naps. Hypersomnia is a symptom of the sleep apnea syndrome, which is a risk factor for cerebrovascular disorders. Daytime sleepiness is also a characteristic symptom of narcolepsy, idiopathic hypersomnia, episodic hypersomnia, and many more neurological or psychiatric disorders; it can also be drug induced. Involvement of brain structures which are essential for the regulation of the sleep wake cycle as a result of neurological disorders can likewise lead to hypersomnia. Symptomatic treatment is necessary when treatment of the causal factors is not possible or no improvement has been achieved.

Austria↗
PubMed1997

Previous treatment as a confounding variable in studies with novel antipsychotics: two cases of high dopamine-2 receptor occupancy with quetiapine.

Previous treatment can be a confounding variable in studies with novel antipsychotics. Quetiapine is a new antipsychotic substance with a low affinity for dopamine-2 (D2) receptors. Preliminary SPECT and PET investigations revealed only a low striatal D2 receptor occupancy rate. However, we present two cases of high striatal D2 receptor occupancy (51% and 71%) measured with 123I IBZM SPECT during quetiapine monotherapy. Both patients had previously received continuous treatment with typical neuroleptics. We present evidence that the previous antipsychotic therapy influenced D2 receptor binding of 123I IBZM during quetiapine treatment weeks after cessation of typical neuroleptics. This might be of importance for the design of clinical trials and brain imaging studies in the future.

Adult↗
PubMed1997

IBZM SPECT imaging of striatal dopamine-2 receptors in psychotic patients treated with the novel antipsychotic substance quetiapine in comparison to clozapine and haloperidol.

We investigated the striatal dopamine-2 (D2) receptor occupancy caused by different antipsychotic substances in 18 psychotic patients (16 with schizophrenic and two with schizoaffective disorder according to DSM-IV) with single photon emission computed tomography (SPECT) using 123I-iodobenzamide (IBZM) as tracer substance. Four patients were treated with the novel antipsychotic compound quetiapine (300-700 mg/day), six with clozapine (300-600 mg/ day) and eight with haloperidol (10-20 mg/day). They were compared with eight healthy controls. Measurement of S/F ratios and consecutive calculation of D2 receptor occupancy revealed a significantly lower striatal D2 occupancy rate with quetiapine and clozapine in comparison to haloperidol. In correspondence with the low striatal D2 receptor occupancy rates and again in contrast to the haloperidol treatment group, there were no extrapyramidal motor side-effects (EPS) in the quetiapine and clozapine treatment groups. Therefore, the reported data support the position that quetiapine can be considered to be an atypical antipsychotic substance due to its relatively weak striatal D2 receptor blocking property and therefore its low propensity to induce EPS.

Adult↗
PubMed1997

Topographic distribution of sleep spindles in young healthy subjects.

The application of an automatic sleep spindle detection procedure allowed the documentation of the topographic distribution of spindle characteristics, such as number, amplitude, frequency and duration, as a function of sleep depth and of recording time. Multichannel all-night EEG recordings were performed in 10 normal healthy subjects aged 20-35 years. Although the interindividual variability in the number of sleep spindles was very high (2.7 +/- 2.1 spindles per minute stage 2 sleep), all but two subjects showed maximal spindle activity in centro-parietal midline leads. Moreover, this topography was seen in all sleep stages and changed only slightly--to a more central distribution--towards the end of the night. On the other hand, slow (11.5-14 Hz) and fast (14-16 Hz) spindles showed a completely different topography, with slow spindles distributed anteriorly and fast spindles centro-parietally. The number of sleep spindles per min was significant depending on sleep stages, with the expected highest occurrence in stage 2, and on recording time, with a decrease in spindle density from the beginning towards the end of the night. However, spindle amplitude, frequency and individual duration was not influenced by sleep depth or time of the night.

Adult↗
PubMed1997

Imaging of dopamine transporters with iodine-123-beta-CIT and SPECT in Parkinson's disease.

UNLABELLED: The aim of the present study was to demonstrate the degeneration of the dopaminergic nigrostriatal pathway in Parkinson's disease by using the cocaine derivative [123I]beta-CIT (2-beta-carbomethoxy-3-beta(4-iodophenyl)-tropane or RTI-55) and SPECT and to relate the findings to the severity of the disease (Hoehn and Yahr scale, H/Y) and to clinical data such as motor score and activities of daily living. METHODS: Thirteen volunteers and 47 patients with idiopathic Parkinson's disease (PD) of H/Y Stage I-V (I:n = 16, II:n = 6, III:n = 14, IV:n = 9, V:n = 2) were investigated. Acquisitions were performed 2, 4, 16, 20 and 24 hr postinjection. ROIs were drawn over the striatum and the cerebellum. Specific beta-CIT binding was defined as striatal minus cerebellar binding. The ratio of specific over nondisplaceable binding (striatum/cerebellum-1) was determined as well as the percent deviation of this ratio from age-expected control values. RESULTS: The time-activity curve of striatal [123I]beta-CIT binding demonstrated a maximum around 20 hr postinjection in controls and a peak 4 hr postinjection in PD patients. Ratios differed significantly between the two groups. A significant correlation existed between this ratio and clinical measures. Hemiparkinsonian patients revealed significantly diminished [123I]beta-CIT binding not only contralateral to the clinically affected but also contralateral to the clinically unaffected side. [123I]beta-CIT binding showed a significant decrease in comparison to age-expected values ranging from 36% in H/Y stage 1 to 71% in H/Y stage V. CONCLUSION: The present study demonstrates that it is possible to visualize and quantify the degeneration of dopaminergic nigrostriatal neurons in PD using [123I]beta-CIT and SPECT with good correlation to clinical parameters.

Adult↗
PubMed1997

Measurement of the dopaminergic degeneration in Parkinson's disease with [123I] beta-CIT and SPECT. Correlation with clinical findings and comparison with multiple system atrophy and progressive supranuclear palsy.

The cocaine derivative [123I] beta-CIT binds with high affinity to dopamine uptake sites in the striatum and can be used to visualize dopaminergic nerve terminals in vivo in the human brain with SPECT. It has been validated that the calculation of a simple ratio of specific/nondisplaceable binding during a period of binding-equilibrium in the striatum about 20 hrs after bolus injection of the tracer gives a strong and reliable index of the binding potential of dopamine uptake sites. Previous studies have shown that the dopaminergic deficit in patients with Parkinson's disease (PD) can clearly be visualized and quantified using this method. Our own results in a group of 113 patients with PD demonstrate a 45% loss of striatal [123I] beta-CIT binding in comparison to age corrected control values. Highly significant correlations of SPECT findings with clinical data obtained from the UPDRS rating scale such as akinesia, rigidity, axial symptoms and activities of daily living are demonstrated, while no correlation is found with tremor. The signal loss in a region comprising the whole striatum ranges from 35% in Hoehn/Yahr stage 1 to over 72% in stage V and is highly significantly correlated to the different stages of disease severity. A comparison of [123I] beta-CIT binding in the striatum contralaterally and ipsilaterally to the affected body side in 29 patients with hemiparkinson shows a loss of striatal binding of 41% contralaterally and 30% ipsilaterally. Results from subregional analyses in caudate and putamen show relative sparing of the caudate nucleus in PD. Data in 9 patients with multiple system atrophy (MSA) and 4 patients with progressive supranuclear palsy (PSP) are similar to the findings in PD although the differences between caudate and putamen are somewhat less marked. These data demonstrate that the dopaminergic nerve cell loss in PD and other disorders with a dopaminergic lesion can be quantified with [123I] beta-CIT and SPECT and that hopefully a preclinical or very early diagnosis is made possible. Such studies might also open the way for a better evaluation of neuroprotective strategies in PD. It does not seem to be possible however to differentiate PD and MSA or PSP with this method in individual cases.

Adult↗
PubMed1997

Iodine-123-epidepride-SPECT: studies in Parkinson's disease, multiple system atrophy and Huntington's disease.

UNLABELLED: Epidepride is a benzamide derivative with very high affinity for D2 receptors, which, in its [123I]-labeled form, can be used for SPECT. The aim of this study was to evaluate the usefulness and accuracy of [123I]epidepride-SPECT for the differential diagnosis of movement disorders. METHODS: SPECT imaging with a triple-headed scintillation camera was performed in 9 patients with Parkinson's disease, 9 patients with probable multiple system atrophy (MSA), 1 patient with progressive supranuclear palsy, 16 patients with Huntington's disease (HD) and 14 controls, 3 hr after the intravenous injection of 3.7 +/- 1.3 mCi of [123I]epidepride. The striatum-to-cerebellum ratio - 1, reflecting the specific-to-nondisplaceable binding ratio, was used as a semiquantitative measure of D2 receptor binding. RESULTS: Kinetic studies showed peak striatal uptake about 3 hr postinjection and a slow decline thereafter. The striatum-to-cerebellum ratio - 1 was significantly reduced in MSA (11.8 +/- 3.9, compared to controls, 19.0 +/- 6.3; p < 0.01) and in patients with HD (8.8 +/- 3.2; p < 0.00005) but normal in Parkinson's disease (15.8 +/- 3.6; not significant). A high interindividual variation of specific striatal epidepride binding (striatum - cerebellum; cpm/mCi x kg) was found in controls and in all patient groups. The interindividual variation of striatum-to-cerebellum ratios was lower but still considerable. In half of the MSA patients, the specific-to-nondisplaceable binding ratio fell within the range of controls. The use of various cortical reference regions did not improve discrimination between MSA and controls or Parkinson's disease patients, respectively. The discrimination of HD patients from controls was better, with overlap in only two cases. In one HD patient, calculation of the striatum-to-cerebellum ratio was almost impossible due to extremely low nonspecific binding. Possible explanations for the large variation of the ratios, resulting in an overlap between controls and different patient groups, are very low counting rates in the reference region and the fact that a transient binding equilibrium may not be achieved after bolus injection of epidepride. CONCLUSION: Epidepride appears to be a useful SPECT ligand for studying dopamine D2 receptors. However, its markedly higher specific-to-nondisplaceable binding ratio in comparison to those of iodobenzamide or other D2 ligands did not result in a better discrimination between different basal ganglia disorders. The calculation of plasma input curves and volumes of distribution might improve the accuracy of [123I]epidepride-SPECT.

Adult↗
PubMed1996

Striatal dopamine-2 receptor occupancy in psychotic patients treated with risperidone.

Seventeen psychiatric patients (11 with schizophrenia, 5 with other psychotic disorders, and 1 with obsessive-compulsive disorder) were examined by single photon emission computed tomography with 123I-iodobenzamide (IBZM) as tracer. Patients were treated with risperidone in two different dosage groups (3 mg and 8 mg) and haloperidol (10-20 mg) and compared with eight healthy control subjects. There was a statistically significant difference in basal ganglia/frontal cortex ratios of IBZM binding between controls and all treatment groups. A statistically significant difference was also found concerning these ratios and percentage of dopamine D2 receptor occupancy rates between the treatment groups with lowest ratios and highest percentage of D2 receptor occupancy in the group of patients treated with haloperidol, followed by the group treated with 8 mg of risperidone and the group treated with 3 mg of risperidone.

Adolescent↗
PubMed1996

Dopamine D2 receptor binding is reduced in Wilson's disease: correlation of neurological deficits with striatal 123I-iodobenzamide binding.

To visualise and quantify dopamine D2 receptor binding in the corpus striatum of patients with neurological Wilson's disease (WD) 123I-Iodobenzamide (IBZM) binding was measured using single photon emission computer tomography (SPECT). Ratios of striatal to frontal countrates were calculated in 8 patients and in 21 healthy control subjects. We found reduced IBZM binding ratios in all patients with WD in comparison to those in controls (1.48 +/- 0.13 vs. 1.73 +/- 0.09). The reduction in IBZM binding was correlated with the overall severity of neurological deficits and the severity of dysarthria (correlation coefficients -0.86 [p < 0.01] and -0.79 [p < 0.01], respectively). When patients of three different subgroups of neurological WD were compared no differences in IBZM binding were found. We conclude that assessing basal ganglia function in vivo using IBZM-SPECT is a valuable diagnostic tool in WD.

Adult↗
PubMed1996

Dopamine D2 receptor imaging in pituitary adenomas using iodine-123-epidepride and SPECT.

UNLABELLED: Epidepride is a novel benzamide derivative with high affinity for D2 receptors. Epidepride, in its 123I-labeled form, can be used for SPECT imaging of striatal and extrastriatal dopamine D2 receptors. The present study evaluated the usefulness of epidepride and SPECT for in vivo imaging of dopamine receptors in pituitary adenomas. METHODS: SPECT imaging was performed in 19 patients with pituitary adenomas (among them 9 patients had prolactinoma, 4 acromegaly, 4 clinically nonfunctioning pituitary adenoma, 1 Cushing's disease and 1 Nelson's syndrome) and 7 control subjects 180 min after intravenous bolus injection of 3.9 +/- 1.1 mCi [123I]epidepride. The ratio target/cerebellum minus 1, reflecting specific/ nonspecific binding was used as semiquantitative measure of D2 receptor binding. RESULTS: Eight of nine prolactinoma patients demonstrated specific binding within the adenoma. The adenoma/ cerebellum ratio 3 hr p.i. showed a wide variation with values from 2.5-33. In three prolactinomas, binding was higher than in the striatum. Specific binding within the lower range of prolactinomas (adenoma/cerebellum ratios 2 and 4.8) could be demonstrated in two of four GH-secreting adenomas. All four nonfunctioning tumors showed specific binding. The adenoma/cerebellum ratio was within the lower range of prolactinomas (5.2-7.5) in three of these patients but extremely high in one (52.3). No specific tracer uptake could be demonstrated in patients with Cushing's disease or Nelson's syndrome. The striatum/cerebellum ratio 3 hr p.i. in pituitary adenoma patients was not significantly different from control subjects (17.3 +/- 5.5 versus 17.8 +/- 6.6; patients versus control subjects). CONCLUSION: Epidepride appears to be an excellent ligand for in vivo imaging of dopamine D2 receptors in pituitary adenomas. Epidepride SPECT could serve as a predictor for response to dopamine agonist treatment.

Acromegaly↗
PubMed1995

A study of acetazolamide-induced changes in cerebral blood flow using 99mTc HMPAO SPECT in patients with cerebrovascular disease.

For semiquantification of SPECT studies we tried to calculate cerebral 99mTc-HMPAO uptake related to injected dose and estimated brain volume. The method was applied to SPECT investigations of 27 patients who had at least one ischaemic attack and a confirmed 80-100% stenosis of the corresponding internal carotid artery (ICA). Vascular reactivity was tested by parenteral administration of acetazolamide (AZ). Increase in HMPAO uptake after AZ was evident in both hemispheres, although the increase (AZ effect) was significantly lower in the affected hemisphere (+24% versus +28%). No interhemispheric uptake differences were seen in patients with largely normal SPECT studies, although local asymmetries in HMPAO deposition were visible. Patients with low density lesions on CT and with a well-demarcated lesion in the same location on SPECT revealed interhemispheric uptake differences, with lower uptake on the affected side. This was not due solely to alterations in the lesion, but also to reduced HMPAO uptake and AZ effect in the surrounding area. The AZ effect showed no correlation with angiographic findings, indicating no major haemodynamic influence of the ICA stenosis on cerebral hemisphere perfusion. Calculated cerebral HMPAO uptake changes after AZ administration were in good accordance with absolute cerebral blood flow measurements, and made interindividual comparisons possible. However, as changes in the area around an infarct or local reduction in vascular reserve may not be reproduced adequately by uptake calculations, visual inspection is still necessary.

Acetazolamide↗
PubMed1995

SPECT imaging of dopamine receptors with [123I]epidepride: characterization of uptake in the human brain.

[123I]Epidepride is a new ligand for single photon emission computerized tomography (SPECT) that specifically labels D2-like dopamine receptors with very high affinity. Here, we report on the regional kinetic uptake of [123I]epidepride in the brain of 4 normal volunteers and 3 patients with choreatic movement disorders. In healthy subjects striatal activity peaked at 2.5 hours after injection of the tracer and decreased slowly thereafter. There were no significant differences between left and right brain hemispheres. Activity above background was also measurable in areas corresponding to the thalamus, temporal cortex and frontal cortex. The striatal to cerebellar ratio was about 14 after 2.5 hours and this ratio steadily increased with time. The striatal to cerebellar ratio was clearly reduced in all 3 patients with choreatic movement disorders (from about 14 in control subjects after 2.5 hours to about 7 in choreatic patients). [123I]Epidepride may be a useful SPECT ligand for studying D2 receptors in the living human brain because of its high target to background ratio, its high affinity and the possibility to investigate extrastriatal D2 receptors.

Adult↗
PubMed1995

beta-CIT SPECT demonstrates blockade of 5HT-uptake sites by citalopram in the human brain in vivo.

The cocaine analogue 2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane (beta-CIT) is a potent ligand for both dopamine- and serotonin uptake sites which in its 123I labeled form can be used for single photon emission computerized tomography (SPECT). It was demonstrated previously by SPECT-studies in non-human primates that 123I-beta-CIT binds to dopamine transporters in the striatum and to serotonin transporters in hypothalamus and midbrain. The aim of the present study was to compare 123I-beta-CIT binding in the brain stem of normal controls and a group of subjects under treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram. 123I-beta-CIT-SPECT was performed in 12 depressed patients under 20 mg (n = 5), 40 mg (n = 6) and 60 mg (n = 1) citalopram daily, in one untreated depressed patient and in 11 controls at regular time intervals up till 24 hours p.inj. A highly significant reduction of beta-CIT binding was found in an area including mesial thalamus, hypothalamus, midbrain and pons in patients under citalopram compared to controls (44.1 +/- 14.4 vs. 82.3 +/- 18.6cpm's/mCi x kg body weight; specific binding 4 hrs p.inj.; p = 0.0001). No differences were seen between the high and low dose group and no changes were found in the striatum. 123I-beta-CIT binding in the brain stem and striatum in one untreated depressed patient fell within the range of control values. To our knowledge this is the first report directly demonstrating the effect of a selective serotonin uptake inhibitor in the brain in humans in vivo. SPECT measurements of serotonin uptake sites in patients with depression and other psychiatric disorders might provide better insights into the pathophysiology of these disorders and into mechanisms of drug action.

Adult↗
PubMed1995

D2 receptor blockade by flunarizine and cinnarizine explains extrapyramidal side effects. A SPECT study.

Twenty-six patients under treatment with the calcium channel blockers flunarizine (Fz) or cinnarizine (Cz) were examined-with single-photon emission computed tomography using [123I]iodobenzamide as a ligand. The striatal dopamine D2 receptor-binding potential was determined and found to be reduced by 14 to 63% (39.5 +/- 15.0%; p < 0.0001) in patients compared with age-matched control values. This reduction was larger in 12 patients with extrapyramidal symptoms and was only slowly reversible after discontinuation of treatment. Patients treated for > 6 months had significantly larger reductions than patients treated for a shorter period. Parkinsonian symptoms were only seen in patients older than 50 years. Our findings prove a neuroleptic-like action of Fz and Cz, which seems to be the major reason for their extrapyramidal side effects. Older age and long-term treatment are predisposing factors for these effects.

Adult↗
PubMed1995

Technetium-99m-HMPAO SPECT imaging of cerebral blood flow during REM sleep in narcoleptics.

UNLABELLED: This study was performed to demonstrate global and regional cerebral blood flow (rCBF) changes during rapid eye movement (REM) sleep in six patients with narcolepsy using SPECT and 99mTc-HMPAO. METHODS: Global and hemispheric HMPAO uptake as well as regional (RI) and asymmetry indices were estimated and compared between polysomnographically verified sleep onset (SO)REM and wakefulness. RESULTS: The estimated global HMPAO uptake did not differ between the two conditions indicating a similar overall cortical activity. During (SO)REM sleep, hemispheric HMPAO uptake as well as calculated RI, especially in the supratemporal plane, were significantly higher on the right side than contralateral. This indicates an initially right-sided cerebral activation and a special involvement of the right, nondominant hemisphere during dreaming which is responsible for visual-spatial perceptions. Furthermore, increased RI in superior parietal regions during sleep were evident and were explained by an activation of associative areas. In thalamic regions, decreased RI were found during sleep, which may reflect thalamic dysfunction. CONCLUSION: A definite assignment of these CBF alterations to (SO)REM sleep might be problematic because of unstable boundaries between sleep stages in narcolepsy. On the other hand, specificity of such CBF changes for narcolepsy requires further study.

Adolescent↗
PubMed1994

Iodine-123-IBZM-SPECT: studies in 15 patients with pituitary tumors.

Single photon emission computerized tomography (SPECT) using the Iodine 123 labeled dopamine D2 receptor antagonist S(-)Iodobenzamide [S (-)IBZM] was performed in 15 patients with pituitary tumors. Among them there were five prolactinoma patients with macroadenoma and two acromegalic patients with macroadenoma. Specific binding in the area of the adenoma was only observed in one subject, a macroprolactinoma patient, who was responsive to dopaminergic treatment. None of the other patients, among them one macroprolactinoma patient responsive to dopaminergic treatment showed specific binding in the area of the tumor. IBZM-binding in the striatum was found to be significantly lower in the group of pituitary tumor patients as compared to controls. The results show that D2 receptors in pituitary adenomas can be visualized using SPECT. However, the sensitivity of IBZM-SPECT appears to be too poor to visualize PRL- and GH- secreting macroadenomas in general.

Adenoma↗