Severe akinetic syndrome resulting from a bilateral basal ganglia lesion following bone marrow transplantation.
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Adult↗
Biomedical subjects
T Brücke
Publications and source records attributed to T Brücke.
In vivo 123I IBZM SPECT imaging of striatal dopamine-2 receptor occupancy in schizophrenic patients treated with olanzapine in comparison to clozapine and haloperidol.
We investigated the degree of striatal dopamine-2 (D2) receptor occupancy in six schizophrenic patients receiving clinically effective antipsychotic treatment with olanzapine 10-25 mg/day in comparison to patients treated with clozapine 300-600 mg/day (n = 6) or haloperidol 5-20 mg/day (n = 10). 123I Iodobenzamide (IBZM) and single photon emission computerized tomography (SPECT) were used for the visualization of striatal D2 receptors. For the quantification of striatal D2 receptor occupancy, striatal IBZM binding in patients treated with antipsychotics was compared to that in untreated healthy controls (n = 8) reported earlier. Olanzapine led to a mean striatal D2 receptor occupancy rate of 75% (range 63-85). Haloperidol-treated patients showed dose-dependently (Pearson r = 0.64; P < 0.05) a significantly higher (P < 0.05) mean occupancy rate of 84% (range 67-94). During clozapine treatment, the mean D2 receptor occupancy of 33% (range < 20-49) was significantly lower than with olanzapine (P < 0.005). The higher striatal D2 receptor occupancy of haloperidol was correlated with the incidence and severity of extrapyramidal motor side-effects (EPS). No clinical relevant EPS occurred during treatment with olanzapine or clozapine. There was no correlation between the degree of striatal D2 receptor occupancy and clinical improvement.
Adult↗
In vivo visualization of serotonin transporters in the human brain during fluoxetine treatment.
Beta-CIT can be used as a tracer for SPECT to visualize serotonin transporters in the human brain. We present a case of bulimia nervosa and major depressive disorder, who had been treated with up to 60 mg/d fluoxetine for several weeks. Four hours after injection of the tracer more than 40% of serotonin transporters were blocked. To our knowledge, this is the first direct documentation of the pharmacodynamic action of fluoxetine in the human brain in vivo.
Adolescent↗
Fatal familial insomnia: a new Austrian family.
We present clinical, pathological and molecular features of the first Austrian family with fatal familial insomnia. Detailed clinical data are available in five patients and autopsy in four patients. Age at onset of disease ranged between 20 and 60 years, and disease duration between 8 and 20 months. Severe loss of weight was an early symptom in all five patients. Four patients developed insomnia and/or autonomic dysfunction, and all five patients developed motor abnormalities. Analysis of the prion protein (PrP) gene revealed the codon 178 point mutation and methionine homozygosity at position 129. In all brains, neuropathology showed widespread cortical astrogliosis, widespread brainstem nuclei and tract degeneration, and olivary 'pseudohypertrophy' with vacuolated neurons, in addition to neuropathological features described previously, such as thalamic and olivary degeneration. Western blotting of one brain and immunocytochemistry in four brains revealed quantitative and regional dissociation between PrP(res)(the protease resistant form of PrP) deposition and histopathology. In the cerebellar cortex of one patient, PrP(res) deposits were prominent in the molecular layer and displayed a peculiar patchy and strip-like pattern with perpendicular orientation to the surface. In another patient, a single vacuolated neuron in the inferior olivary nuclei contained prominent intravacuolar granular PrP(res) deposits, resembling changes of brainstem neurons in bovine spongiform encephalopathy.
Adult↗
Imaging the pre- and postsynaptic side of striatal dopaminergic synapses in idiopathic cervical dystonia: a SPECT study using [123I] epidepride and [123I] beta-CIT.
There is increasing evidence that a dysfunction of the dopaminergic system may be involved in the pathogenesis of idiopathic dystonia. To visualize possible alterations of the pre- and postsynaptic side of striatal dopaminergic synapses, SPECT studies using the radiotracers [123I] epidepride and [123I] beta-CIT were performed in 10 patients with idiopathic cervical dystonia. Eleven age- and sex-matched subjects served as controls. [123I] Epidepride is a new highly affine marker of D2 receptors, and [123I] beta-CIT binds to dopamine transporters on dopaminergic nerve endings. [123I] Epidepride binding was significantly reduced in both striata of dystonia patients compared with controls (p < 0.05). In contrast, striatal [123I beta-CIT uptake did not differ from controls. We conclude that dopaminergic dysfunction in idiopathic focal dystonia mainly involves postsynaptic mechanisms and suggest a disturbance of the indirect pathway of the motor circuit resulting in a disinhibited thalamocortical stimulation.
Adult↗
Sertindole and dopamine D2 receptor occupancy in comparison to risperidone, clozapine and haloperidol - a 123I-IBZM SPECT study.
The striatal D2 dopamine binding was studied in schizophrenic patients treated with the novel atypical antipsychotic drug sertindole (n=10). Comparisons were obtained with haloperidol (n=8), clozapine (n=6), risperidone (n=11) and untreated healthy controls (n=8) of a dataset which has partly been reported previously. 123I-Iodobenzamide (IBZM) single photon emission computerized tomography (SPECT) was used for estimation of striatal dopamine D2 receptor binding. Sertindole-treated patients exhibited significantly (P < 0.001) lower levels of striatal D2 binding (BG/FC ratio:1.28) compared with those treated with haloperidol (BG/FC ratio:1.09) and risperidone (8 mg:1.18) but significantly (P < 0.005) higher levels compared with clozapine (BG/FC ratio: 1.49). However, if patients were pretreated with a depot neuroleptic, significantly (P < 0.05) higher striatal D2 binding (BG/FC ratio:1.12) has been obtained. Since sertindole has been shown to exert distinct clinical efficacy for treatment of positive and negative symptoms, our data are indicative that antipsychotic efficacy is not associated with a high degree of striatal D2 receptor occupancy in schizophrenic patients.
Adult↗
[123I]beta-CIT and SPECT in essential tremor and Parkinson's disease.
UNLABELLED: Resting and postural tremor may occur in essential tremor (ET) and Parkinson's disease (PD). The aim of the present study was to investigate the cocaine derivative [123I]beta-CIT, which labels striatal dopamine transporters, and SPECT in differentiating these diseases. METHODS: 30 healthy volunteers, 32 patients with ET and 29 patients with idiopathic PD of Hoehn/Yahr stage I were investigated. Specific over nondisplaceable binding ratios (target/cerebellum-1) were calculated for the striatum, the caudate nucleus and the putamen separately as well as a ratio putamen/caudate and the percent deviation of each patient's ratio from age-expected control values. RESULTS: Striatal [123I]beta-CIT binding ratios in ET were within normal ranges and showed only a discrete elevation to age-expected control values (+14.6%). In PD significantly reduced specific binding was evident not only contralaterally to the clinically affected side (putamen: -62%, caudate nucleus: -35%), but also ipsilaterally (putamen: -45%, caudate nucleus: -22%). All investigated parameters differed significantly between PD and controls and ET respectively. CONCLUSION: Imaging striatal dopamine transporters with [123I]beta-CIT and SPECT could clearly distinguish between ET and PD in an early stage of the disease. Findings do not suggest a subclinical involvement of dopaminergic nigrostriatal neurons in ET.
Adult↗
Acute porphyric neuropathy during pregnancy--effect of haematin therapy.
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Acute Disease↗
Imaging of cerebral blood flow with technetium-99m-HMPAO and technetium-99m-ECD: a comparison.
UNLABELLED: Because 99mTc-HMPAO and 99mTc-ECD are both used for SPECT imaging of cerebral blood flow, the question arises whether there are any differences in their respective regional cerebral distribution. For that purpose, visual and semiquantitative comparisons between 99mTc-HMPAO and 99mTc-ECD studies were performed. METHODS: Seventeen patients (4 women; 13 men; age 45-89 yr; mean age 71 yr) with various neurological diseases, except acute/subacute stroke, were investigated twice with 99mTc-HMPAO and 99mTc-ECD using a triple-headed rotating SPECT camera. After image reorientation, the two studies were evaluated visually. Seventy regions of interest (ROIs) were drawn manually and the same set of ROIs was applied in both studies. Regional indices (RI) normalized to individual brain values were calculated and first compared between two random patient groups. Second, for all patients, RI for 70 and later for 27 regions (gained after summing values of corresponding regions in different brain slices) were compared by using a paired Student's t-test applying Bonferroni's correction. RESULTS: Visual evaluation demonstrated relatively high 99mTc-ECD uptake in occipital and comparatively low uptake in mediotemporal regions. Calculation of RI revealed significantly higher values in the right cerebellum, brainstem, mediotemporal regions, right basal ganglia and the thalamus in the 99mTc-HMPAO SPECT studies and higher values in the occipital, supratemporal/inferior parietal and parietal cortex in the 99mTc-ECD SPECT studies, respectively. CONCLUSION: Significant differences in regional tracer distribution between 99mTc-HMPAO and 99mTc-ECD could be detected, probably caused by different tracer kinetics. The results indicate that direct comparisons of studies performed with 99mTc-HMPAO and 99mTc-ECD are not possible and the use of either tracer can be favorable in different clinical questions.
Aged↗
[123I]beta-CIT single-photon emission tomography in DOPA-responsive dystonia.
The radiotracer [123I]beta-CIT is a sensitive marker of dopamine uptake sites that can be used to visualize dopaminergic nerve endings in vivo in the human brain. We report on [123I]beta-CIT single-photon emission computed tomography (SPECT) findings in a patient with DOPA-responsive dystonia (DRD). [123I]beta-CIT SPECT showed a striatal radiotracer uptake in the upper range of normal, indicating intact dopamine transporters and structural integrity of nigrostriatal neurons. This differentiates DRD from clinically similar cases with juvenile-onset parkinsonism with dystonia that have a considerable poorer prognosis. [123I]-beta-CIT SPECT may provide a method equally as useful as fluorodopa positron emission tomography in DRD.
Adult↗
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↗
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↗
Olfactory functions in Parkinson's disease and Alzheimer's disease.
The aim of this investigation was to compare olfactory functions of patients suffering from Parkinson's disease (PD) and Alzheimer's disease (AD). Olfactory threshold, odor identification ability and odor memory performance were assessed in 21 non-demented PD patients and in 22 AD patients. Both patient groups were impaired in relation to an age-matched control group for the measure of odor identification. AD patients showed a higher olfactory threshold and poorer odor memory performance.
Aged↗
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↗
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↗
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↗
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↗