Presynaptic Dopaminergic Dysfunction Research Articles

Differences in [123I]Ioflupane Striatal Binding Between African American and White Patients.

Ethnic differences exist among patients with Parkinson disease (PD). PD is more common in the White than the African American population. This study aimed to explore whether differences exist in [123I]ioflupane binding, which reflects dopamine transporter binding, between African American and White individuals. Methods: Medical charts were reviewed for patients who underwent [123I]ioflupane SPECT imaging as part of routine practice in a single academic medical center. All images were visually graded as showing normal or abnormal presynaptic dopaminergic function (normal or abnormal scan status). Quantitative [123I]ioflupane uptake as measured by the specific binding ratios in the right and left striata and their subregions (caudate nucleus and anterior and posterior putamen) and by bilateral putamen-to-caudate ratios were compared between African American and White patients using multiple linear regression adjusted for age, sex, and abnormal scan status. Additional models included an ethnicity-by-abnormal-scan-status interaction term to determine whether abnormal scan status was modulated by ethnicity effect. Results: The percentage of patients with abnormal scan status was comparable between African American and White patients. Compared with White patients (n = 173), African American patients (n = 82) had statistically significantly higher uptake as measured by specific binding ratios in the right and left striata and some of their subregions (right and left caudate nuclei and right posterior putamen). Ethnicity-by-abnormal-scan-status interactions were not statistically supported for any models. Conclusion: We observed differences in [123I]ioflupane binding between African American and White patients independent of presynaptic dopaminergic dysfunction status. Future studies are needed to examine whether and how ethnicity affects dopamine transporter binding activities and its clinical relevance.

Assessing impulse control behaviors in early Parkinson's disease: a longitudinal study.

Impulse control behaviors (ICBs) frequently coexist with Parkinson's disease (PD). However, the predictors of ICBs in PD remain unclear, and there is limited data on the biological correlates of ICBs in PD. In this study, we examined clinical, imaging, and biological variables to identify factors associated with longitudinal changes in ICBs in early-stage PD. The data for this study were obtained from the Parkinson's Progression Markers Initiative, an international prospective cohort study that evaluates markers of disease progression in PD. We examined clinical, imaging, and biological variables to determine their associations with ICBs over a period of up to 5 years. Cox regression models were employed to investigate the predictors of ICBs in early-stage, untreated PD. The study enrolled 401 individuals with PD and 185 healthy controls (HC). At baseline, 83 PD subjects (20.7%) and 36 HC (19.5%) exhibited ICBs. Over the course of 5 years, the prevalence of ICBs increased in PD (from 20.7% to 27.3%, p < 0.001), while it decreased in HC (from 19.5% to 15.2%, p < 0.001). Longitudinally, the presence of ICBs in PD was associated with depression, anxiety, autonomic dysfunction, and excessive daytime sleepiness (EDS). However, there was no significant association observed with cognitive dysfunction or motor severity. Treatment with dopamine agonists was linked to ICBs at years 3 and 4. Conversely, there was no association found between ICBs and presynaptic dopaminergic dysfunction. Additionally, biofluid markers in baseline and the first year did not show a significant association with ICBs. A predictive index for ICBs was generated, incorporating three baseline characteristics: anxiety, rapid eye movement sleep behavior disorder (RBD), and p-tau levels in cerebrospinal fluid (CSF). During the early stages of PD, there is a notable increase in ICBs over time. These ICBs are associated with depression, anxiety, autonomic dysfunction, EDS, and the use of dopaminergic medications, particularly dopamine agonists. Anxiety, RBD, and p-tau levels in CSF are identified as predictors for the incident development of ICBs in early PD. Further longitudinal analyses will provide a more comprehensive understanding of the associations between ICBs and imaging findings, as well as biomarkers. These analyses will help to better characterize the relationships and implications of these factors in the context of ICBs in early PD.

Presynaptic Dopaminergic Dysfunction Was Overestimated in Huntington's Disease Presenting as Young Age-Onset Parkinsonism.

Presynaptic Dopaminergic Dysfunction Was Overestimated in Huntington's Disease Presenting as Young Age-Onset Parkinsonism.

Prenatal hypoxia alters the early ontogeny of dopamine neurons

Dopaminergic (DA) dysfunction is a significant feature in the pathophysiology of schizophrenia. Established developmental risk factors for schizophrenia such as maternal immune activation (MIA) or developmental vitamin D (DVD) deficiency, when modelled in animals, reveal the differentiation of early DA neurons in foetal brains is delayed suggesting this may be a convergent aetiological pathway. Here we have assessed the effects of prenatal hypoxia, another well-known developmental risk factor for schizophrenia, on developing DA systems. Pregnant mice were exposed to a hypoxic environment of 10% oxygen for 48 h from embryonic day 10 (E10) to E12. Embryonic brains were collected and the positioning of mesencephalic cells, expression of DA specification and maturation factors were examined along with the expression of factors that may govern the migration of these neurons. We show that prenatal hypoxia results in a decrease in dopaminergic progenitors retards early DA neuron lateral migration and reduces expression of the receptors known to govern this process. A second time-point, postnatal day 10 (P10) was also examined in order to assess whether prenatal hypoxia alters early presynaptic architecture in the developing striatum. We show reduced expression of tyrosine hydroxylase (TH) in the postnatal striatum along with increases in the density of high-probability DA release sites within TH varicosities. These findings add to the emerging literature showing that multiple epidemiologically validated environmental risk factors for schizophrenia may induce early alterations to develop DA systems. This may represent a possible convergent mechanism in the onset of presynaptic DA dysfunction in patients.

Radioiodination and Purification of [131I]β-CIT and [131I]FP-CIT with an Automated Radiosynthesizer.

Dopaminergic transporter (DAT) imaging with single photon emission computed tomography (SPECT) is used to diagnose Parkinson’s disease and to differentiate it from other neurodegenerative disorders without presynaptic dopaminergic dysfunction. The radioiodinated tropane alkaloids [123I]FP-CIT and [123I]β-CIT enable the evaluation of the integrity of DATs. Commonly, the labeling of these compounds is performed by electrophilic substitution of the alkylstannylated precursors with radioactive iodine and following purification by HPLC or solid phase extraction (SPE). This work presents the first radioiodination of β-CIT and FP-CIT with no carrier added [131I]NaI on a Scintomics GRP synthesis module. Free iodine-131 and impurities were removed by SPE over a C-18 Sep-Pak cartridge. We achieved a radiochemical yield of >75% and a radiochemical purity of >98% with both compounds. Our development of an automated synthesis on a commercially available synthesizer ensures robust and efficient labeling of [131I]FP-CIT and [131I]β-CIT starting with low concentrated radioiodine.

A Retrospective Imaging Evaluation of Presynaptic Dopaminergic Degeneration in Multiple System Atrophy with Levodopa Induced Dyskinesia

Background:Multiple system atrophy (MSA) may develop levodopa-induced dyskinesia, which is dystonic and predominant in the orofacial region. We aimed to characterize the patterns of presynaptic dopaminergic degeneration in patients with MSA and dyskinesia using 123I-N-x-fluoropropyl-2b-carbo-methoxy-3b-(4-iodophenyl) nortropan single-photon emission computed tomography (123I-FP-CIT SPECT).Methods:A single center cross-sectional retrospective study was conducted using consecutive chart review of patients with probable MSA who underwent 123I-FP-CIT SPECT. The degeneration patterns were compared between the groups with and without dyskinesia via visual assessment of 123I-FP-CIT SPECT images.Results:Twenty-five patients with probable MSA who had undergone dopamine transporter imaging were identified (age [mean ± standard error], 62.5 ± 1.7 years; disease duration, 48.8 ± 7.0 months). Four of them presented dyskinesia and 21 of patients did not. Twenty-five patients with MSA were visually classified into five grades: one Grade 1 (normal), two Grade 2 (eagle wing), three Grade 3 (mixed), nine Grade 4 (egg shape), and ten Grade 5 (burst striatum). All patients with MSA and dyskinesia were classified into Grade 5. Visual grading significantly correlated with disease duration and levodopa responsiveness.Conclusions:Severe presynaptic dopaminergic dysfunction in 123I-FP-CIT SPECT images, higher doses of dopaminergic medication, and longer disease durations were associated with occurrence of levodopa-induced dyskinesia, even in MSA.

Dysphagia is associated with presynaptic dopaminergic dysfunction and greater non-motor symptom burden in early drug-naïve Parkinson's patients.

BackgroundThe underlying pathophysiology of dysphagia is multifactorial and evidence clarifying the precise mechanisms are scarce. Dysfunction in dopamine-related and non-dopamine-related pathways, changes in cortical networks related with swallowing and peripheral mechanisms have been implicated in the pathogenesis of dysphagia. We aimed at investigating whether dysphagia is associated with presynaptic dopaminergic deficits, faster motor symptom progression and cognitive decline in a population of early drug-naïve patients with Parkinson’s disease.MethodsBy exploring the database of Parkinson’s Progression Markers Initiative we identified forty-nine early drug-naïve Parkinson’s disease patients with dysphagia. Dysphagia was identified with SCOPA-AUT question 1 (answer regularly) and was assessed with MDS-UPDRS Part-II, Item 2.3 (Chewing and Swallowing). We compared Parkinson’s disease patients with dysphagia to Parkinson’s disease patients without dysphagia, and investigated differences in striatal [123I]FP-CIT single photon emission computed tomography levels. Using Cox proportional hazards analyses, we also evaluated whether dysphagia can predict motor deterioration and cognitive dysfunction.ResultsParkinson’s disease patients with dysphagia, harbored a greater deterioration regarding motor and non-motor symptoms and decreased [123I]FP-CIT binding when compared with patients without dysphagia. Higher burden of dysphagia (MDS-UPDRS-II, item 2.3) was correlated with lower [123I]FP-CIT uptakes within the striatum (rs = −0.157; P = 0.002) and the caudate (rs = −0.156; P = 0.002). The presence of dysphagia was not a predictor of motor progression (Hazard ratio [HR]: 1.143, 95% confidence interval [CI]: 0.848–1.541; P = 0.379) or cognitive decline (HR: 1.294, 95% CI: 0.616–2.719; P = 0.496).ConclusionsDysphagia is associated with decreased presynaptic dopaminergic integrity within caudate and greater motor and non-motor symptoms burden in early drug-naïve PD.

Technetium-99m Labeled Tropane Derivative: Uptake in a Pituitary Macroadenoma.

We present a case of suspected idiopathic Parkinson's disease in whom extrastriatal accumulation of Technetium-99m labeled tropane derivatives in a pituitary macroadenoma interfered with image quality and interpretation. Subsequent F-18 fluoro-dihydroxyphenylalanine positron emission tomography/computed tomography was useful to demonstrate the absence of presynaptic dopaminergic dysfunction.

43.4 THE ROLE OF MOLECULAR IMAGING IN GUIDING DRUG DEVELOPMENT

BackgroundMolecular imaging with Positron Emission Tomography (PET) has the unique capability of examining molecules in the brains of human subjects in real time. This has been well exploited in the study of dopaminergic transmission in schizophrenia. The results have on one hand confirmed some predictions, and on the other hand they have brought up unexpected findings, that have the potential to affect drug development in a major way.MethodsPET studies of dopamine release, synthesis, storage, receptors and transporters across labs and different experiments will be reviewed to extract findings that differ from preconceived notions. These have the capability of re-focusing drug development based on new evidence.ResultsExpected findings that PET studies have confirmed are those of striatal dopaminergic excess, measured as enhanced presynaptic release capacity and presynaptic enzymatic synthesis capacity. Also expected was hypodopaminergic transmission in the dorso-lateral prefrontal cortex.The unexpected findings from PET have been as follows: 1) the striatal excess is most predominant in the associative striatum, rather than the limbic striatum. 2) hypodopaminergia is generalized to all extrastriatal areas of the brainThese observations of opposite presynaptic dopaminergic dysfunction between striatal and extrastriatal regions suggest that the striatal excess may not be driven by activity levels of midbrain DA cells but may result from abnormal striatal local regulation of presynaptic DA release, affecting specifically the associative striatum, region which shows largest magnitude of excess DA. Furthermore alterations in dopaminergic signaling in opposing directions may have a dual effect on learning across functional domains by weakening learning from salient or relevant signals and reinforcing stimulus independent signals, thus explaining different symptom domains.DiscussionMore work is needed to understand the cellular mechanisms of dopaminergic dysfunction in schizophrenia. The evidence presented here, while limited, highlights the challenges of drug development in the absence of real in vivo information from patients, and the need for multidisciplinary cross talk to address these challenges.

18F]FDOPA positron emission tomography in manganese-exposed workers

Occupational manganese (Mn) exposure is associated with the development of parkinsonism; however, the mechanism of neurotoxicity is unknown. Brain positron emission tomography (PET) imaging provides a non-invasive method of assessing dopamineric neuronal function. 6-[18F]fluoro-L-DOPA (FDOPA) PET reflects in-vivo nigrostriatal function, but results in Mn exposure are conflicting. The objective of this study was to investigate the association between Mn exposure secondary to occupational welding, FDOPA striatal uptake, and clinical parkinsonism as measured by Unified Parkinson Disease Rating Scale motor subscore 3 (UPDRS3) scores. FDOPA PET scans were acquired on 72 subjects (27 Mn-exposed welders, 14 other Mn-exposed workers, and 31 non-exposed subjects). We estimated cumulative welding exposure from detailed work histories, and a movement disorders specialist examined all subjects. Striatal volumes of interest were identified on aligned magnetic resonance imaging (MRI) for each subject. Specific striatal FDOPA uptake was calculated with a graphical analysis method. We used linear regression while adjusting for age to assess the association between welding exposure and FDOPA uptake in the caudate, anterior putamen, and posterior putamen. Compared to the non-exposed subjects, mean caudate FDOPA uptake was 0.0014min−1 (95% confidence interval [CI] 0.0008, 0.0020) lower in Mn-exposed welders and 0.0012min−1 (95% CI 0.0005, 0.0019) lower in other Mn-exposed workers (both p≤0.001). There was no clear dose-response association between caudate FDOPA uptake and Mn exposure or UPDRS3 scores. Mn-exposed welders and workers demonstrated lower caudate FDOPA uptake, indicating pre-synaptic dopaminergic dysfunction in Mn-exposed subjects that was not associated with clinical parkinsonism.

123I-FP-CIT SPECT imaging in blepharospasm

IntroductionBlepharospasm is a focal dystonia characterized by involuntary cocontraction of the eyelid protractors, causing spasmodic closure of the eyelids. Apraxia of eyelid opening is caused by an inability to initiate lid opening without paralytic abnormality. Some studies suggest that patients with either pure blepharospasm or blepharospasm associated with apraxia of eyelid opening are more prone to developing Parkinson's disease. MethodsIn our study, 123I-FP-CIT (DAT) SPECT was performed in 24 patients with either pure blepharospasm or blepharospasm associated with apraxia of eyelid opening and no signs of parkinsonism to identify dopaminergic dysfunction. ResultsDAT-SPECT was abnormal in 11 (46%) cases (five patients with isolated blepharospasm and six patients with blepharospasm associated with apraxia of eyelid opening) whose mean disease duration was 11 years. ConclusionOur study revealed presynaptic dopaminergic dysfunction, as determined by 123I-FP-CIT or DAT-SPECT, in nearly half of our blepharospasm patients (with or without apraxia of eyelid opening). Thus, the presence of blepharospasm might be an early sign of a parkinsonian syndrome.

Longitudinal assessment of excessive daytime sleepiness in early Parkinson’s disease

BackgroundExcessive daytime sleepiness (EDS) is common and disabling in Parkinson’s disease (PD). Predictors of EDS are unclear, and data on biological correlates of EDS in PD are limited. We investigated...

Tc-99m TRODAT uptake in an osteoid tumor of clivus.

Tc-99m TRODAT is cocaine analog and binds to the dopamine transporter in vivo. Tc-99m TRODAT single-photon emission computed tomography/computed tomography. (SPECT/CT) is useful for demonstrating presynaptic dopaminergic dysfunction in patients with Parkinsonism. However, few reports have shown extrastriatal uptake of Tc-99m TRODAT. We present the case of a 67-year-old male who underwent Tc-99m TRODAT SPECT/CT for evaluation of Parkinsonism. In addition to tracer binding in the striatum, tracer uptake was noted in an osteoid tumor of the clivus. Integrated SPECT/CT enabled precise localization and characterization of the extrastriatal site of tracer binding and emphasizes the importance of such coincidental findings.

Optimizing diagnosis in Parkinson's disease: Radionuclide imaging

Parkinson's disease (PD) and other disorders characterized by basal ganglia dysfunction are often associated with limited structural imaging changes that might assist in the clinical or research setting. Radionuclide imaging has been used to assess characteristic functional changes. Presynaptic dopaminergic dysfunction in PD can be revealed through the imaging of different steps in the process of dopamine synthesis and storage: L-aromatic amino acid decarboxylase (AADC) activity, Vesicular Monoamine Transporter type 2 (VMAT2) binding or its reuptake via the dopamine transporter (DAT). Postsynaptic dopamine dysfunction can also be studied with a variety of different tracers that primarily assess D2-like dopamine receptor availability.The function of other neurotransmitters such as norepinephrine, serotonin and acetylcholine can be imaged as well, giving important information about the underlying pathophysiologic process of PD and its complications. The imaging of metabolic activity and pathologic changes has also provided great advances in the field.Together, these techniques have allowed for a better understanding of PD, may be of aid for differentiating PD from other forms of parkinsonism and will undoubtedly be useful for the establishment of new therapeutic targets.

Substantia nigra echogenicity is correlated with nigrostriatal impairment in Machado-Joseph disease

BackgroundSeveral studies have demonstrated increased substantia nigra (SN) echogenicity in Parkinson's disease (PD) and Machado-Joseph disease (MJD). Pathological substrate of PD is characterized by dopaminergic nigrostriatal cell loss, also found in MJD. Also, SN hyperechogenicity might be associated with nigrostriatal dysfunction in PD, when comparing dopamine transporter binding with SN echogenicity. The present study aimed to correlate the SN echogenic size and striatal dopamine transporter density in MJD patients. MethodsWe performed TCS in 30 subjects and SPECT with [99mTc]-TRODAT-1 in 18 subjects with MJD. Fifteen healthy subjects matched for age and gender formed a control group. TCS and [99mTc]-TRODAT-1 SPECT findings from both MJD patients and control subjects were compared. ResultsThere were no differences regarding age (p = 0.358) or gender (p = 0.566) between groups (MJD versus control group). Mean DAT binding potentials and SN echogenicity were significantly different between groups. There was a significant negative correlation with regard to the SN echogenic size and the ipsilateral striatal TRODAT-1 uptake: the higher the SN echogenicity, the lower the DAT uptake in the ipsilateral cerebral hemisphere. ConclusionIncrease in SN echogenic size likely correlates with presynaptic dopaminergic nigrostriatal dysfunction in MJD, suggesting a concurrent in vivo pathophysiological mechanism.

From the Prodrome to Chronic Schizophrenia: The Neurobiology Underlying Psychotic Symptoms and Cognitive Impairments

Schizophrenia is a chronic psychotic disorder that remains a considerable cause of global disease burden. Cognitive impairments are common and contribute significantly to the morbidity of the disorder. Over the last two decades or so molecular imaging studies have refined understanding of the pathophysiology underlying the development of psychosis and cognitive impairments. Firstly they have consistently implicated presynaptic dopaminergic dysfunction in the disorder, finding that dopamine synthesis capacity, dopamine release and baseline dopamine levels are increased in the illness. Secondly recent findings show that dopamine synthesis capacity is elevated in those that go on to develop psychosis in the following year, but not in those that do not, and appears to increase further with the development of psychosis. Thirdly evidence links greater dopamine synthesis capacity to poorer cognitive performance and altered frontal cortical function measured using functional imaging during cognitive tasks. Finally they have provided data on the nature of other neurofunctional alterations in the disorder, in particular in the serotonergic system and neuroinflammation. We review these findings and discuss their implications for understanding the neurobiology of psychosis and cognitive impairments in schizophrenia.

Pupillometry and 123I-DaTSCAN imaging in Parkinson's Disease: A Comparison Study

ABSTRACTThe purpose of this study was the evaluation of pupil light reflex (PLR) in patients with Parkinson's disease (PD) by using a modern pupillometry system and the investigation of its potential relationship with dopamine transporter imaging (DaTSCAN), which is an objective method for the evaluation of presynaptic dopaminergic system. PLR was evaluated using pupillometry in 35 patients with PD without clinical evidence of autonomic dysfunction and 44 healthy matched controls. PLR was elicited using a fully automated pupillometry system and six parameters were measured. Dopamine transporter imaging was performed using radioactive ioflupane 123I-FP-CIT [123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)-nortropane]. A significant increase in latency and a significant decrease in amplitude, maximum constriction velocity, as well as maximum acceleration were observed in PD patients. There was no significant difference in initial radius and minimum radius values. Investigating the relationship between pupillometry parameters and 123I-FP-CIT binding values, we correlated values from the semiquantitative analysis of radioligand uptake with pupillometry parameters, but we found no significant correlation. This study demonstrates PLR impairment in patients with PD without overt autonomic dysfunction. This impairment does not seem to correspond to the reduction of radioligand binding in the striatum as the result of presynaptic dopaminergic dysfunction, suggesting a different deterioration rate of these systems.

Clinical significance of the pallidoreticular pathway in patients with carbon monoxide intoxication

Whereas globus pallidus lesions resulting from carbon monoxide intoxication have been extensively described in the literature, the clinical significance of pallidoreticular lesions has rarely been mentioned. This study incorporated information from functional and structural imaging to explore the correlations of pallidoreticular lesions with parkinsonian features and neurobehavioural performance. Twenty-five patients (11 males) with globus pallidus lesions after carbon monoxide intoxication and 25 age- and sex-matched controls were enrolled for detailed neurological examinations, cognitive testing, susceptibility weighted imaging, diffusion tensor imaging and 99mTc-TRODAT-1 single photon emission computed tomography. The post-processing analysis of the neuroimaging included voxel-based morphometry to assess the regional atrophy, tract-based spatial statistics related to white matter involvement, tractography to investigate the rostral and caudal projections from the midbrain level and specific uptake ratios of 99mTc-TRODAT-1 for presynaptic dopaminergic transporter activity. In susceptibility weighted imaging, low-intensity pallidoreticular lesions were detected from the minimal-intensity projections, which were visible in only 7.7% of the T(1)-weighted images and 15.4% of the T(2)-weighted images, whereas inhomogeneous intensities were detected in the globus pallidus. The patients were further divided into two subgroups based on the presence (n = 13) or absence (n = 12) of pallidoreticular lesions. The patients with pallidoreticular lesions showed increased parkinsonian features, poorer performances on the neuropsychiatric tests, lower 99mTc-TRODAT-1 availability in both the caudate and the putamen and greater atrophy of the thalamus, posterior corpus callosum, cerebral peduncle and white matter surrounding the globus pallidus compared to those without pallidoreticular lesions. The tractography results obtained with seed regions of interest in the substantia nigra showed rostral projections to the supplementary motor cortex and anterior cingulate cortex via the globus pallidus; the two pathways were distinct but ran in parallel, caudal to the level of the globus pallidus. In conclusion, the presence of pallidoreticular lesions after carbon monoxide intoxication indicates a poorer cognitive state, which is associated with extensive grey and white matter damage in addition to the damage to the nigra-striatal neuronal networks. The presence of parkinsonian features may be related to pallidal and presynaptic dopaminergic dysfunction. The sensitivity for detecting pallidoreticular lesions can be greatly improved by using susceptibility weighted imaging compared with conventional imaging.

Dopamine Synthesis Capacity Before Onset of Psychosis: A Prospective [18F]-DOPA PET Imaging Study

While there is robust evidence of elevated dopamine synthesis capacity once a psychotic disorder has developed, little is known about whether it is altered prior to the first episode of frank illness. The authors addressed this issue by measuring dopamine synthesis capacity in individuals at ultra-high risk of psychosis and then following them to determine their clinical outcome. This prospective study included 30 patients who met standard criteria for being at ultra-high risk of psychosis and 29 healthy volunteers. Participants were scanned using [(18)F]6-fluoro-L-dopa positron emission tomography. The ultra-high-risk patients were scanned at presentation and followed up for at least 3 years to determine their clinical outcome. Six patients had comorbid schizotypal personality disorder and were excluded from the analysis (data are provided for comparison). Of the remaining patients, nine developed a psychotic disorder (psychotic transition group) and 15 did not (nontransition group). There was a significant effect of group on striatal dopamine synthesis capacity. The psychotic transition group had greater dopamine synthesis capacity in the striatum (effect size=1.18) and its associative subdivision (effect size=1.24) than did the healthy comparison subjects and showed a positive correlation between dopamine synthesis capacity and symptom severity. Dopamine synthesis capacity was also significantly greater in the psychotic transition group than in the nontransition group. These findings provide evidence that the onset of frank psychosis is preceded by presynaptic dopaminergic dysfunction. Further research is needed to determine the specificity of elevated dopamine synthesis capacity to particular psychotic disorders.

123I] FP-CIT SPECT in Creutzfeldt–Jakob disease

A 79-year-old man presented with rapidly progressive, mildly fluctuating, dementia which started 2.5 months previously. Clinical examination confirmed cognitive deficit, dominated by apathy and mutism, and showed a symmetric extrapyramidal syndrome without tremor. Metabolic analyses (including thyroid function, antithyroid autoantibodies, and paraneoplastic antibodies) were normal. Brain MRI, performed 1.5 months after symptom onset, was normal. Electroencephalopgram (EEG) showed diffuse slowing. Cerebrospinal fluid analysis revealed a mildly elevated protein level without pleiocytosis. [I] FP-CIT SPECT, in search of arguments in favour of dementia with Lewy bodies (DLB), showed bilateral decreased presynaptic dopaminergic function predominant in the head of the caudate nucleus (Fig. 1). A possible diagnosis of DLB was evoked although visual hallucinations and REM sleep behaviour disorder lacked. Three weeks later, the patient developed asynchronous upper limb myoclonus. This time, brain MRI showed increased signal on DWIand FLAIR-weighted imaging in the cortex and the deep grey matter, predominant in the left hemisphere (Fig. 2). EEG revealed periodic 1 Hz biand triphasic sharp waves with left-sided predominance (Fig. 2). In the mean time, cerebrospinal fluid 14-3-3 protein analysis was performed and showed increased levels. A diagnosis of probable Creutzfeldt–Jakob disease (CJD) was made. [F] FDG PET showed hypometabolism in the fronto-parieto-temporal cortex and the basal ganglia, predominant in the left hemisphere (Fig. 2). The symptoms worsened rapidly and the patient died 7 weeks after admission. Few data exist on FP-CIT SPECT in CJD. Only one CJD case has been reported, describing asymmetric reduced presynaptic dopaminergic function predominant in the putamen [1]. Since both extrapyramidal syndrome and MRI signal changes in the basal ganglia are often seen in CJD, dopaminergic dysfunction on functional brain imaging seems to not be unexpected. Presynaptic dopaminergic dysfunction in Parkinson’s disease and DLB is most often predominant in the putamen. In our