SPECT and PET imaging of the dopaminergic system in Parkinson's disease.

This paper gives an overview of the clinical importance of SPECT and PET imaging of the dopaminergic system in the differential diagnosis and for the determination of the progression rate of Parkinson's disease (PD). D2 receptor imaging can help to differentiate multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) from PD. In patients treated with neuroleptics it is possible to determine the rate of striatal D2 receptor blockade using this technique. This occupancy rate parallels the occurrence of parkinsonian side effects. Its measurement helps in the selection of newer atypical neuroleptics, which can be used to treat drug-induced psychosis in PD because they do not aggravate parkinsonian symptoms. Imaging of dopaminergic neurons with [123I]beta-CIT SPECT or [18F]DOPA PET is a way to visualize and quantify the nigrostriatal dopaminergic lesion in PD. Findings correlate with clinical rating scales and demonstrate the feasibility of detecting the preclinical lesion in patients with hemiparkinson or familial PD. [123I]beta-CIT SPECT can easily distinguish patients with essential tremor and patients with "lower body parkinsonism" due to a subcortical vascular encephalopathy. MSA and PSP cannot be separated from PD with this method alone. Longitudinal studies with [123I]beta-CIT SPECT and [18F]DOPA PET can quantify the progression rate in PD. SPECT results from our own group show a low rate of progression in patients with a long duration of disease and a more marked progression rate in patients with shorter disease duration. In the former group regions in the striatum with higher beta-CIT binding at the time of the first SPECT scan decline faster than regions with lower binding. These findings suggest a curvilinear course of progression which starts at different time points in different striatal regions and which levels off after several years of disease duration. These findings are in line with data from PET studies and underline the importance of an early start of neuroprotective strategies. Preliminary data from PET and SPECT studies in early PD suggest that dopamine agonists might have a slight neuroprotective effect and might slow down the rate of progression of the disease.

Regional cerebral blood flow during temporal lobe seizures associated with ictal vomiting: an ictal SPECT study in two patients.

PURPOSE: Ictal vomiting represents a rare clinical manifestation during seizures originating from the temporal lobes of the nondominant hemisphere. The precise anatomic structures responsible for generation of ictal vomiting remain to be clarified. Ictal single photon emission computed tomography (SPECT), which allows one to visualize the three-dimensional dynamic changes of regional cerebral blood flow (rCBF) associated with the ongoing epileptic activity, should be useful to study the brain areas activated during ictal vomiting. METHODS: We performed ictal Tc-HMPAO SPECT scans in two patients with mesial temporal lobe epilepsy (MTLE) whose seizures were characterized by ictal retching and vomiting. MTLE was documented by typical clinical seizure semiology, interictal and ictal EEG findings, hippocampal atrophy on magnetic resonance imaging (MRI) scan, and a seizure-free outcome after selective amydalohippocampectomy. In both patients, seizures originated in the nondominant temporal lobe. We obtained accurate anatomic reference of rCBF changes visible on SPECT by a special coregistration technique of MRI and SPECT. We used ictal SPECT studies in 10 patients with MTLE who had seizures without ictal vomiting as controls. RESULTS: In the two patients with ictal vomiting, we found a significant hyperperfusion of the nondominant temporal lobe (inferior, medial, and lateral superior) and of the occipital region on ictal SPECT. In patients without ictal vomiting, on the contrary, these brain regions never were hyperperfused simultaneously. CONCLUSIONS: Ictal SPECT provides further evidence that activation of a complex cortical network, including the medial and lateral superior aspects of the temporal lobe, and maybe the occipital lobes, is responsible for the generation of ictal vomiting.

Preictal SPECT in temporal lobe epilepsy: regional cerebral blood flow is increased prior to electroencephalography-seizure onset.

UNLABELLED: Peri-ictal SPECT provides unique information on the dynamic changes in regional cerebral blood flow (rCBF) that occur during seizure evolution and, thus, could be useful in clarifying the poorly understood interplay of the interictal and ictal states in human focal epilepsy. The regional hyperperfusion observed on ictal SPECT is generally believed to be a consequence of electrical seizure activity. However, recent studies using invasive long-term cortical CBF monitoring have demonstrated that rCBF changes occur up to 20 min prior to ictal electroencephalography (EEG) onset. Because of apparent technical difficulties, no preictal SPECT studies have been reported so far. Therefore, we present our results on two patients with temporal lobe epilepsy in whom preictal SPECT scans were performed fortuitously under continuous video-EEG monitoring control. METHODS: Technetium-99m-hexamethyl propyleneamine oxime was injected 11 min (Patient 1) and 12 min (Patient 2) before clinical and EEG seizure onset, as documented from simultaneous video-EEG monitoring in two patients with temporal lobe epilepsy. We obtained accurate anatomical reference of CBF changes visible on SPECT by a special coregistration technique of MRI and SPECT. RESULTS: Whereas interictal SPECT showed a hypoperfusion of the temporal lobe ipsilateral to the seizure focus, on preictal SPECT, a significant increase in rCBF in the epileptic temporal lobe could be observed. These rCBF changes were not accompanied by any significant changes of the ongoing EEG. CONCLUSION: Our study provides evidence that rCBF is increased in the epileptic temporal lobe several minutes before EEG seizure onset. Thus, rCBF changes observed on peri-ictal SPECT scan cannot be considered a mere consequence of EEG seizure activity but may rather reflect a change in neuronal activity precipitating the transition from the interictal to the ictal state.

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.

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.

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.

[Presurgical diagnosis of epilepsy and surgical epilepsy treatment]. / Prächirurgische Epilepsiediagnostik und operative Epilepsietherapie.

20% of patients with focal epilepsy suffer from medically refractory seizures. Many of these patients can be cured by a surgical intervention removing the brain area where the seizures are originating (epileptogenic zone). 6000 patients in Austria would benefit from epilepsy surgery with an additional 150-200 new patients appearing each year. Potential candidates have to undergo an extensive presurgical work-up. During the non-invasive Phase I each patient is evaluated with an intensive video-EEG monitoring with scalp-EEG, a high resolution MRI, a SPECT and/or PET, a neuropsychological evaluation and a Wada-test. If the epileptogenic zone cannot be localized adequately with these methods, invasive electrophysiological techniques (epidural Peg-electrodes, Foramen-ovale electrodes, depth electrodes, subdural strip and grid electrodes) have to be applied. Operative strategies for temporal lobe epilepsies include antero-mesial temporal lobe resections and selective amygdala-hippocampectomies. Extratemporal epilepsies are treated by cortical resections guided by structural and electrophysiological parameters. The new technique of multiple subpial transections facilitates treatment of seizures originating in essential brain regions. Catastrophic epilepsies of early childhood often are caused by extensive pathologies affecting one hemisphere and can be treated successfully by large multilobar resections or hemispherectomies. Epilepsy surgery renders 70-80% of patients seizure free and thus can be regarded as an effective and safe treatment option for patients with medically refractory focal epilepsies.

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.

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.

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.

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.

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.

Epileptic negative myoclonus: An EEG-single-photon emission CT study indicating involvement of premotor cortex.

We report a combined EEG-single-photon emission CT (SPECT) study on a patient with epileptic negative myoclonus (ENM). Clinically, the ENM was characterized by brief repetitive lapses in postural tone of the right upper extremity when the arms were held outstretched, whereas no movement effect was observed during rest. Ictal EEG showed repetitive left frontal spikes with a maximum at electrodes EC1 and F1. EMG silent periods lasting from 100 to 200 ms followed the onset of the EEG transients by a latency of 20 to 40 ms. The N20 component of median nerve somatosensory evoked potentials-representing a biological marker of the location of central fissure-showed a phase reversal between electrodes P3 and C1 and thus was located considerably posterior to the spike maximum. We obtained accurate anatomic reference of cerebral blood flow changes visible on SPECT by a special coregistration technique of MRI and SPECT. SPECT performed during ENM showed a marked regional hyperperfusion in the left middle frontal gyrus and a less pronounced increase in tracer uptake in the left supramarginal gyrus. Our results suggest that ENM is generated by epileptic activity in the premotor area in the middle frontal gyrus corresponding to Brodmann's area 6.

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.

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.

Nicergoline in senile dementia of Alzheimer type and multi-infarct dementia: a double-blind, placebo-controlled, clinical and EEG/ERP mapping study.

In a double-blind, placebo-controlled study on the therapeutic efficacy and central effects of nicergoline, an ergot alkaloid with metabolic, antithrombotic and vasoactive action, 112 patients with mild to moderate dementia, diagnosed according to DSM III-R criteria (MMS 13-25), living in pensioners' homes, were included. Fifty-six were subdiagnosed as senile dementia of the Alzheimer type (SDAT), 56 as multiinfarct dementia (MID), based on computed tomography and Hachinski scores (< or = 49 SDAT, > or = 7 MID). They received, after 2 weeks' run-in period (placebo), randomized for 8 weeks either 2 x 30 mg nicergoline (NIC) or 2 x 1 placebo (PLAC) orally. The four subgroups (SDAT/NIC. SDAT/PLAC, MID/NIC, MID/PLAC; 4 x 28 patients) were comparable in regard to age and sex. Only four, four, four and two patients of the respective groups did not finish the study for minor reasons. Confirmatory statistical analysis demonstrated in the target variable-the Clinical Global Impression (CGI)-a significant superiority of Global Impression (CGI)-a significant superiority of NIC over PLAC in both the SDAT and MID groups. Global improvement (CGI item 2) was seen in both nicergoline subgroups (3 and 3), while no changes occurred under placebo (4 and 4, respectively). The responder versus non-responder ratio was in the SDAT/NIC group 16/8, versus 8/16 in the SDAT/PLAC group (chi 2 = 4.1, P = 0.04); in the MID/NIC group 17/7, versus 7/19 in the MID/PLAC group (chi 2 = 7.96, P < 0.005). Furthermore, there was a significant improvement of the Mini-Mental State and the SCAG score in both the MID and SDAT group after 8 weeks of nicergoline, which was significantly superior to the minimal improvement or no change in placebo-treated SDAT and MID patients. EEG mapping demonstrated in NIC-treated SDAT and MID patients a significant decrease in delta and theta, increase in alpha 2 and beta activity and an acceleration of the centroid of the total power spectrum as compared with pretreatment, while opposite changes occurred in PLAC-treated SDAT and MID patients. The differences between PLAC and NIC reached the level of statistical significance. Event-related potential (ERP) recordings demonstrated a significantly shortened P300 latency under NIC treatment in both SDAT and MID patients, while there was a trend towards lengthening under PLAC. Thus, nicergoline improved vigilance and information processing at the neurophysiological level, which leads at the behavioural level to clinical improvement both in degenerative and vascular dementia.

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.

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.

Chronic relapsing polyradiculoneuropathy in IgG lambda monoclonal gammopathy of undetermined significance (MGUS)--complete remission following carmustine treatment.

A previously healthy 43 year-old female developed IgG lambda monoclonal gammopathy of undetermined significance (MGUS) and ascending sensorimotor polyradiculoneuropathy which relapsed 11 times within 2 years. Marked improvement was noted repeatedly after plasmapheresis. However, on each occasion symptoms and signs of polyradiculoneuropathy recurred almost exactly 3 weeks after plasma-pheresis. Following 6 weeks of treatment with carmustine (70 mg/week), nearly complete recovery was established, which has persisted up to now (82 months after the end of therapy). The close temporal correlation between clinical relapse and recurrence of the IgG paraprotein and its permanent absence in stable clinical remission after carmustine treatment suggest a causal relationship between the paraprotein and the polyradiculoneuropathy. However, further studies are required to confirm this observation, as well as the efficacy of carmustine therapy.