PET studies on the memory processing of word pairs in bilingual Finnish-English subjects.

This study examined the fundamental question whether verbal memory processing in two unrelated languages is mediated by a common neural system or by distinct cortical areas. Ten right-handed, male Finnish--English adult late bilinguals who had acquired the second language after the age of 10 were scanned whilst either encoding/retrieving word pairs in their mother tongue (Finnish) or in a foreign language (English). Within each language, subjects had to encode and retrieve four sets of 12 visually presented paired word associates which were not semantically related. Two sets consisted of highly imageable words (e.g. monkey-table; koira-lasi) and the other two sets of abstract word pairs (e.g. freedom-moral; uhka-suure). Presentation of pseudowords served as a reference condition. An emission scan was recorded after each intravenous administration of O-15 water. Encoding was associated with prefrontal and hippocampal activation. During memory retrieval, precuneus showed a consistent activation in both languages and for both highly imageable and abstract words. Although the brain mechanisms of the two languages share common components, differential activations were found in Broca's area and in the cerebellum as well as in the angular/supramarginal gyri according to the language used.

Positron emission tomography shows that impaired frontal lobe functioning in Parkinson's disease is related to dopaminergic hypofunction in the caudate nucleus.

We examined the relation between the dopaminergic function and the cognitive performance of patients with Parkinson's disease (PD). The subject sample consisted of ten patients in the early course of PD and with no previous antiparkinsonian medication. The dopaminergic function of the caudate nucleus and the putamen was studied with [(18)F]fluorodopa positron emission tomography, and the cognitive performance with a comprehensive battery of neuropsychological tests including tests sensitive to frontal lobe function. The decreased [(18)F]fluorodopa uptake in the right caudate nucleus was found to be related to slow processing time, measured as the difference between the incongruent and the congruent subtests of the Stroop Test (r=-0.85, P=0.002), a similar trend was seen in the left caudate (r=-0.60, P=0.07). Similar correlation was not detected in the putamen. The present findings provide evidence that the decreased dopaminergic function in the right caudate nucleus is related to the impaired performance in tests sensitive to frontal lobe function in patients at an early stage of PD and with no antiparkinsonian medication.

EFNS Task Force on Teaching of Neuroimaging in Neurology Curricula in Europe: present status and recommendations for the future.

A Task Force on 'Teaching of Neuroimaging in Neurology Curricula in Europe' was appointed in September 1998 by the education committee of the European Federation of Neurological Societies (EFNS) in order to: (1) examine the present status of teaching of neuroimaging in the training of neurology in European countries, and, in particular, to assess the strengths and weaknesses of the various countries; (2) give recommendations for global improvement and harmonization of such training. A questionnaire was completed in February 1999 and sent to 35 delegates of national neurological societies. Completed questionnaires were received from 21 countries: Albania, Austria, Croatia, Czech Republic, Denmark, Estonia, Finland, Germany, Greece, Hungary, Israel, Italy, Netherlands, Norway, Poland, Portugal, Slovakia, Spain, Switzerland, Turkey and UK. The questionnaire revealed that the situation in Europe is highly heterogeneous, both as regards the training in neurology in general and, more specifically, the teaching of neuroimaging during the training. Some recommendations to make the teaching of neuroimaging more homogeneous across European countries and to improve it are provided.

Risk for Parkinson's disease: twin studies for the detection of asymptomatic subjects using [18F]6-fluorodopa PET.

Positron emission tomography (PET) studies were carried out with [18F]6-fluorodopa ([18F]6-FD) in monozygotic (MZ) and dizygotic (DZ) twins for the clarification of dopaminergic function. Four MZ and four DZ pairs of twins, each pair consisting of a parkinsonian index case and an asymptomatic co-twin, were collected from the Nationwide Twin Cohort. The control group comprised 14 healthy volunteers. [18F]6-FD PET examinations with a Siemens/CTI 931/08 scanner were performed dynamically over 90 min. The regions-of-interest analysis included the caudate, the putamen and the occipital reference regions. Patlak plots were calculated using occipital tissue input function. The accumulation of [18F]6-FD in the putamen of the asymptomatic co-twins was significantly lower than that in the normal subjects. This result implies that there may be a preclinical stage of Parkinson's disease in the apparently normal co-twins at the time of the PET study.

Striatal dopamine D1 receptors in narcolepsy: a PET study with [11C]NNC 756.

We investigated dopamine D1 receptors in the putamen and caudate nucleus with positron emission tomography in six patients with narcolepsy and five healthy controls using [11C]NNC 756 as ligand. The caudate-to-cerebellum and putamen-to-cerebellum ratios of [11C]NNC 756 were within normal limits in patients with narcolepsy. No evidence of increased D1 receptor binding in narcolepsy was found.

Increased density of dopamine D2 receptors in the putamen, but not in the caudate nucleus in early Parkinson's disease: a PET study with [11C]raclopride.

Striatal dopamine D2 receptors were studied, using positron emission tomography (PET), in 10 patients with early Parkinson's disease without any antiparkinsonian medication and in 14 healthy controls. [11C]Raclopride was used as ligand and an equilibrium method was applied. The maximum count of receptors (Bmax) and their dissociation constant (Kd) were calculated according to the Scatchard principle. In parkinsonian patients, the Bmax of D2 receptors was increased in the putamen contralateral to the predominant symptoms, as compared to the opposite putamen, by 33% (p = 0.0008). In the caudate nucleus no significant side to side differences was noted. On comparison with age-matched healthy controls, Bmax values in the putamen (p = 0.0012) but not in the caudate nucleus contralateral to the side of predominant clinical symptoms were increased in PD patients. The Kd values were unchanged. The difference in putaminal Bmax values between the opposite hemispheres correlated with the difference in the severity of parkinsonian motor symptoms between the two body sides (r = 0.69, p = 0.03). The present results show that there is both a relative and absolute increase in the number of dopamine D2 receptors in the putamen, but not in the caudate nucleus in early Parkinson's disease.

PET examination of the monoamine transporter with [11C]beta-CIT and [11C]beta-CFT in early Parkinson's disease.

The monoamine transporter was studied in 4 healthy controls and 5 patients with early Parkinson's disease (PD), who had not received any antiparkinsonian medication, by means of positron emission tomography (PET) using two novel ligands, [11C]beta-CIT and [11C]beta-CFT. Both ligands showed highest uptake in the striatum. There was intermediate accumulation of activity in the thalamus and midbrain, which was more marked for [11C]beta-CIT than for [11C]beta-CFT. In the cortical areas, uptake of both ligands was not different from that seen in the cerebellum. In the controls, the putamen-to-cerebellum and caudate-to-cerebellum ratios for [11C]beta-CFT were higher than those for [11C]beta-CIT (putamen: 3.15 +/- 0.39 for [11C]beta-CFT, and 1.84 +/- 0.10 for [11C]beta-CIT; caudate: 3.15 +/- 0.31 for [11C]beta-CFT, and 1.95 +/- 0.17 for [11C]beta-CIT). Reduction from mean control value in PD patients was greater for [11C]beta-CFT (45% in the putamen contralateral to the predominant symptoms, P < 0.001) than for [11C]beta-CIT (20%, P > 0.05). [11C]beta-CFT uptake in the caudate nucleus was also diminished in PD patients (to 80% of the control mean, P < 0.05), whereas [11C]beta-CIT was within normal range (reduced to 90% of the control mean). These results indicate that both [11C]beta-CIT and [11C]beta-CFT are useful PET ligands to study brain monoamine transporter in healthy controls and in patients with PD. However, [11C]beta-CFT seems superior to [11C]beta-CIT in this respect.

Positron emission tomography study of human narcolepsy: no increase in striatal dopamine D2 receptors.

We investigated dopamine D2 receptors in the caudate nucleus and putamen with positron emission tomography in seven patients with narcolepsy and seven healthy controls by using [11C]raclopride as a ligand. We applied an equilibrium method and Scatchard principle to give a quantitative estimation of the number (Bmax) and dissociation constant (Kd) of the receptors. Both the Bmax and Kd were within the normal range in the caudate nucleus and putamen in narcoleptic patients. We found no evidence for increased D2 receptor binding in narcolepsy.

PET studies on brain monoamine transporters with carbon-11-beta-CIT in Parkinson's disease.

UNLABELLED: The cocaine analog 2 beta-carbomethoxy-3 beta-[4-iodophenyl]tropane (beta-CIT) labeled with 11C was used to study dopamine reuptake sites with PET. METHODS: Three normal subjects and nine patients with Parkinson's disease were investigated. Each of them underwent a dynamic PET scan (25 timeframes over 80 min) with [11C]-beta-CIT. A dose of 102.5-211.3 MBq (2.77-5.71 mCi) of this ligand was administered intravenously and a PET examination with an ECAT 931/08 PET camera was carried out. Ratios between the striatal/cortical/thalamic/midbrain and cerebellar uptake of this radioligand were calculated. RESULTS: The highest accumulation of [11C]beta-CIT was observed in the caudate and putamen, though there was some uptake in the thalamus and the midbrain. Cortical uptake was negligible. Carbon-11-beta-CIT accumulated significantly less in the putamen of the Parkinson's patients than in the normal subjects. The putamen-to-cerebellum ratio in the Parkinson's patients was 1.59 +/- 0.04 and 1.80 +/- 0.13s (p = 0.028) in the normal subjects. In the caudate, there was no significant difference between the Parkinson's patients and the normal subjects. CONCLUSION: These results imply that [11C]beta-CIT is a useful compound for carrying out a PET examination of the function of the presynaptic monoaminergic neurons both in normal and pathological brains.

Striatal [18F]fluorodopa utilization after COMT inhibition with entacapone studied with PET in advanced Parkinson's disease.

The effect of peripheral catechol-O-methyltransferase (COMT) inhibition with entacapone on striatal uptake of 6-[18F]fluoro-L-dopa (FDOPA) was studied with PET both without and with entacapone in fifteen advanced parkinsonian patients and six healthy controls. Entacapone significantly enhanced the fraction of unmetabolized FDOPA in plasma from 16% to about 50% at 80 minutes after FDOPA injection in all subjects. The striatal to occipital ratios and the striatal FDOPA uptake, expressed as a modified decarboxylation coefficient (k3R0), was significantly increased in healthy controls, whereas in parkinsonian patients the increase was significant only in the caudate. On the other hand, the influx constant (Ki) decreased significantly in the caudate and putamen in parkinsonian patients; in healthy controls the Ki remained virtually unchanged. Effective peripheral COMT inhibition markedly increased the fraction of FDOPA in plasma and thus its availability in the brain for decarboxylation both in patients and control subjects. However, the change in striatal FDOPA uptake was modest in the advanced parkinsonian patients as compared to that in control subjects, because of the advanced disease, decreased storage capacity, or both.

PET studies on dopamine D1 receptors in the human brain with carbon-11-SCH 39166 and carbon-11-NNC 756.

UNLABELLED: PET studies were carried out on brain dopamine D1 receptors using two new ligands, [11C]SCH 39166 and [11C]NNC 756. METHODS: Four normal subjects and eight predominantly unilateral patients with early Parkinson's disease were investigated. Each of them underwent both a PET scan with [11C]SCH 39166 and one with [11C]NNC 756. A dose of about 185 MBq (5 mCi) of these ligands was administered intravenously and a dynamic PET scan with an ECAT 931/08 PET camera was carried out. Ratios between the striatal and cerebellar uptake of these compounds were calculated. RESULTS: Both [11C]SCH 39166 and [11C]NNC 756 accumulated in the striatum. There was also some neocortical binding; 75% of the striatal value in the case of [11C]SCH 39166 and 60% with [11C]NNC 756 which displayed higher (p < 0.01) uptake in the striatum than [11C]SCH 39166. There were no significant side-to-side differences in the controls nor in the parkinsonian patients. CONCLUSIONS: These results imply that both [11C]SCH 39166 and [11C]NNC 756 can be used in PET studies for the visualization and quantification of dopamine D1 receptors. Since [11C]NNC 756 has a significantly better signal-to-noise ratio in the striatum than [11C]SCH 39166, it seems to offer definite advantages for studies of D1 receptors.

PET study on striatal dopamine D2 receptor changes during the progression of early Parkinson's disease.

[11C]Raclopride uptake to dopamine D2 receptors was investigated with positron emission tomography (PET) in patients with early Parkinson's disease at the time of the diagnosis and after a half-year interval. During this progressive period of the disease, the patients received no antiparkinsonian medication. The upregulation of striatal D2 receptors, which was seen in all patients already at the time of the diagnosis, persisted. Although the patients initially showed unilateral disease, they had developed bilateral symptoms by the time of the second PET scan, but the disease was still asymmetric. The present results show that the relative increase in [11C]raclopride uptake in the striatum contralateral to the symptoms as compared with the opposite striatum will be preserved even during the progression of the disease, provided that the symptoms show clear-cut asymmetry.

Decrease in human striatal dopamine D2 receptor density with age: a PET study with [11C]raclopride.

The effect of age on human striatal dopamine D2 receptors was investigated with positron emission tomography (PET) using [11C]raclopride as a radioligand. Twenty-one healthy volunteers aged from 20 to 81 years were studied. An equilibrium method was applied and two separate PET scans with different specific activities of [11C]raclopride were performed. The maximal number of receptors (Bmax) and their dissociation constant (Kd) were calculated using Scatchard analysis. There was an age-dependent decline in the Bmax (r = -0.49; p = 0.02) of striatal D2 receptors while the Kd remained unchanged. The results show that there is an age-related loss of striatal D2 receptors, which, together with other changes in the brain nigrostriatal dopaminergic system, may contribute to extrapyramidal symptoms associated with aging.

Comparison of lisuride and bromocriptine in the treatment of advanced Parkinson's disease.

Twenty patients with advanced idiopathic Parkinson's disease were studied, all having a deteriorating response to levodopa and suffering from daily fluctuations in disability. A double-blind randomized cross-over study was conducted. Basic levodopa and anticholinergic treatment was continued unchanged in all patients. The dose increment period of 4-8 weeks was followed by a 4 week treatment period on a fixed optimal dose. In both treatment groups the mean optimal daily dose of lisuride was 1.3 mg (range 0.2-2.4 mg) and that of bromocriptine about 15 mg (range 3.75-30.0), without any significant differences between the treatment groups. The addition of lisuride or bromocriptine to levodopa treatment resulted in a significant and equal further improvement of parkinsonian disability. The therapeutic profiles of both lisuride and bromocriptine were similar. There was significantly more improvement in tremor than in other parkinsonian symptoms. Both lisuride and bromocriptine elicited a significant improvement in fluctuations of disability. No significant differences between the treatments were observed. The occurrence of clinical side effects seemed to be similar with both treatment regimens. In advanced parkinsonian patients the therapeutic efficacy of lisuride seems to be equal to that of bromocriptine as far as parkinsonian disability and fluctuations in disability are concerned.

[18F]-6-fluorodopa PET scanning in Parkinson's disease after selective COMT inhibition with nitecapone (OR-462).

PET studies were performed to investigate the effects of a new cathechol-O-methyltransferase (COMT) inhibitor, nitecapone (OR-462 [3-(3,4-dihydroxy-5-nitrobenzylidene)- 2,4-pentadione]), on the accumulation of dopamine in the striatum and whether it is able to improve [18F]6-fluorodopa imaging of the brain. Altogether, three patients with Parkinson's disease (PD) and three normal volunteers were examined, first without nitecapone and then with an oral dose of 100 mg of nitecapone 1 hour before the IV injection of 3 mCi of [18F]6-fluorodopa. High-pressure liquid chromatography analysis of arterial plasma samples showed a significant reduction in the metabolic conversion rate from [18F]6-fluorodopa to [18F]3-O-methylfluorodopa after the administration of nitecapone. PET studies showed that nitecapone significantly (p less than 0.05) increased the [18F]6-fluorodopa accumulation in the striatum both in PD patients and normal controls; the magnitude of this increase was 20.0 +/- 5.5% (mean +/- SEM). The ratio of radioactivity in the striatum and arterial plasma was increased 39.0 +/- 5.0% (mean +/- SEM) after the administration of nitecapone. Consequently, the quality of PET images after OR-462 was better, which has implications for future [18F]6-fluorodopa studies. In addition, COMT inhibition may have clinical advantages by improving levodopa treatment in PD.

A post-mortem study on striatal dopamine receptors in Parkinson's disease.

Striatal dopamine D1 and D2 receptors were investigated in 49 patients with Parkinson's disease (PD) and 33 age-matched controls with [3H]SCH 23390 and [3H]spiroperidol as ligands respectively. A full Scatchard analysis giving Bmax and Kd values was performed. In the caudate nucleus, a small but significant decrease in the number of D1 and D2 receptors was seen, whereas in the putamen the number of dopamine receptors was unchanged. Treatment with neuroleptics was found to increase the number of D2 receptors both in the caudate nucleus and putamen. The number of neither D1 nor D2 receptors correlated neither with the duration of disease or levodopa treatment of the patients nor with the post-mortem delay or storage time of the samples. Furthermore, no association was found between either D1 or D2 receptor number and clinical variables of the patients. The activity of choline acetyltransferase (ChAT) was found to be unchanged in the striatum, whereas a marked decline was seen in the hippocampus and cortical areas, indicating that intrinsic striatal cholinergic neurons are not affected in PD. The present results suggest that there is a modest decline in the number of striatal dopamine D2 receptors in advanced patients with PD at the end stage of the disease.

Assessment of psychiatric and psychosocial factors disposing to chronic outcome of dermatoses.

In many skin diseases, itching and scratching is a vicious circle, which prolongs the disease. The aim of this study was to investigate the mechanisms which make itching skin diseases more chronic. The patients consisted of seven diagnostic groups--79 inpatients all together. The dermatoses were: dermatitis herpetiformis, lichen ruber planus, chronic eczema, atopic eczema, neurodermatitis circumscriptus, prurico psychogenous and lichen obtusus corneus. Both psychiatric and dermatological examinations were performed. Psychiatric disturbance was clearly greater than in the average population. The chronifying mechanisms were the following: personality disorder as a treatment problem; emotional infantility, which makes the illness itself an important security factor; itching and scratching as pleasure and content of life; the accumulation of various other diseases, both somatic and psychiatric; and untreated depression. Information was obtained on the possibilities of psychiatric treatment and psychosocial rehabilitation.

PET demonstrates different behaviour of striatal dopamine D-1 and D-2 receptors in early Parkinson's disease.

Striatal dopamine D-1 receptor binding was investigated in vivo with positron emission tomography (PET) in five patients with early Parkinson's disease using [11C]-SCH 23390. All patients had predominantly unilateral symptoms and showed a significant reduction in the accumulation of [18F]-6-F-DOPA in the striatum contralateral to the symptoms. None of the patients had received any antiparkinsonian medication. The striatal and cerebellar radioactivity was measured and corresponding striatum/cerebellum ratios were counted. The mean striatum/cerebellum ratio of [11C]-SCH 23390 binding was symmetric between the hemispheres. By contrast, the striatum/cerebellum ratio of [11C]raclopride binding, labelling dopamine D-2 receptors, was increased significantly in the hemisphere contralateral to the symptoms as compared with the opposite hemisphere. Thus, the present results show that the behaviour of striatal D-1 and D-2 receptors is different in early Parkinson's disease.