Dopa Uptake Research Articles

Accuracy of [18F]Fluorodopa Positron Emission Tomography for Diagnosing and Localizing Focal Congenital Hyperinsulinism

Focal lesions in infants with congenital hyperinsulinism (HI) represent areas of adenomatosis that express a paternally derived ATP-sensitive potassium channel mutation due to embryonic loss of heterozygosity for the maternal 11p region. This study evaluated the accuracy of 18F-fluoro-l-dihydroxyphenylalanine ([18F]DOPA) positron emission tomography (PET) scans in diagnosing focal vs. diffuse disease and identifying the location of focal lesions. A total of 50 infants with HI unresponsive to medical therapy were studied. Patients were injected iv with [18F]DOPA, and PET scans were obtained for 50-60 min. Images were coregistered with abdominal computed tomography scans. PET scan interpretations were compared with histological diagnoses. The diagnosis of focal or diffuse HI was correct in 44 of the 50 cases (88%). [18F]DOPA PET identified focal areas of high uptake of radiopharmaceutical in 18 of 24 patients with focal disease. The locations of these lesions matched the areas of increased [18F]DOPA uptake on the PET scans in all of the cases. PET scan correctly located five lesions that could not be visualized at surgery. The positive predictive value of [18F]DOPA in diagnosing focal adenomatosis was 100%, and the negative predictive value was 81%. [18F]DOPA PET scans correctly diagnosed 75% of focal cases and were 100% accurate in identifying the location of the lesion. These results suggest that [18F]DOPA PET imaging provides a useful guide to surgical resection of focal adenomatosis and should be considered as a guide to surgery in all infants with congenital HI who have medically uncontrollable disease.

Progressive changes of pre‐ and post‐synaptic dopaminergic biomarkers in conscious MPTP‐treated cynomolgus monkeys measured by positronemission tomography

Positron emission tomography (PET) is a useful technique for the consecutive investigation of the relationship between changes in neurotransmission biomarkers and behavioral signs in animal models of Parkinson's disease (PD). In this study, we aimed to investigate the threshold of dopamine (DA) neuron damage for the appearance of tremor by observing the longitudinal changes of pre- and post-synaptic DA biomarkers in awake monkeys using PET with multiple tracers. Three cynomolgus monkeys were treated with MPTP every 3-6 weeks until tremor was observed. Brain uptake of [11C]PE2I, [beta-11C]DOPA, and [11C]raclopride for DA transporter (DAT), DOPA utilization, and DA D2 receptor were measured using PET as a single set in awake condition. Sets of PET scans were repeated in parallel with continuous behavioral estimation. The pre-synaptic biomarkers of DA neuron in the striatum decreased [11C]PE2I binding and [beta-11C]DOPA uptake in an MPTP dose-dependent manner. Tremor was not observed until striatal [11C]PE2I binding was reduced to about 15% of the pretreatment level and [beta-11C]DOPA uptake was reduced to about 34%. DA D2 receptor measured by [11C]raclopride was not significantly changed throughout the experiment. Our results revealed that it is possible to quantitatively define the threshold of the onset of behavioral PD signs by monitoring spontaneous motor activity, and in vivo PET with DAT marker can be a biomarker for early diagnosis at the presymptomatic stage of PD and for high-risk groups.

Dopaminergic function in depressed patients with affective flattening or with impulsivity: [ 18F]Fluoro- l-dopa positron emission tomography study with voxel-based analysis

A decreased striatal presynaptic dopaminergic function has been reported in depressed patients with affective flattening and psychomotor retardation, using 18F-fluorodopa positron emission tomography and regions-of-interest. The present study aimed to investigate regional `[ 18F]dopa uptake in mesolimbic and mesocortical dopaminergic projections with the hypothesis that there should be a decrease in mesolimbic [ 18F]dopa uptake associated with affective flattening and psychomotor retardation. [ 18F]Dopa-positron emission tomography and anatomical magnetic resonance imaging datasets from 12 screened depressed patients with either marked affective flattening and psychomotor retardation ( n = 6) or with marked impulsivity ( n = 6), and from eight healthy subjects, were analyzed using a voxel-based approach. Regional differences in [ 18F]dopa uptake rate constant ( K i) values between the healthy group and the two depression subgroups were compared using both statistical parametric mapping and cluster-based regions-of-interest. Patients with affective flattening and psychomotor retardation had [ 18F]dopa K i decreases in the left caudate, bilateral putamen and nucleus accumbens, left parahippocampus and dorsal brainstem. Impulsive depressives had [ 18F]dopa K i decreases in the anterior cingulate and hypothalamus, and an increase in the right parahippocampal gyrus. These findings support distinct regional dysfunctions of monoamines depending on the depressive symptomatology.

Diagnosis and Localization of Focal Congenital Hyperinsulinism by 18F-Fluorodopa PET Scan

To assess the accuracy of 18F-fluoro-L-dihydroxyphenylalanine ([18F]-DOPA) PET scans to diagnose focal versus diffuse disease and to localize focal lesions in infants with congenital hyperinsulinism. Twenty-four infants with hyperinsulinism unresponsive to medical therapy were studied. Patients were injected intravenously with [18F]-DOPA, and PET scans were obtained for 1 hour. Images were coregistered with abdominal CT scans. The diagnosis of focal or diffuse hyperinsulinism was correct in 23 of the 24 cases (96%) and equivocal in 1 case. [18F]-DOPA PET identified focal areas of high uptake of radiopharmaceutical in 11 patients. Pathology results confirmed that all 11 had focal adenomatosis, and the locations of these lesions matched the areas of increased [18F]-DOPA uptake on the PET scans in all of the cases. [18F]-DOPA PET scans were 96% accurate in diagnosing focal or diffuse disease and 100% accurate in localizing the focal lesion. These results suggest that [18F]-DOPA PET imaging should be considered in all infants with congenital hyperinsulinism who need to have pancreatectomy.

Striatal subregional 6‐[18F]fluoro‐L‐dopa uptake in early Parkinson's disease: A two‐year follow‐up study

Thirty-one drug-naive patients with Parkinson's disease (PD) underwent 6-[18F]fluoro-L-dopa (F-dopa) positron emission tomography (PET) scan at the time of the diagnosis (baseline) and 2 years later in order to investigate F-dopa uptake in striatal and extrastriatal regions during the first years of early PD. Twenty-four healthy controls underwent one F-dopa PET scan. The regional differences in the striatal and extrastriatal regions were analyzed with statistical parametric mapping and automated region of interest analyses. Our study shows that the F-dopa uptake in unmedicated early PD is most severely decreased in the dorsal part of caudal putamen but significant decrease can be seen throughout the striatum compared with controls. During the first years of PD, there is a progressive regional decline in striatal F-dopa uptake, the dorsal part of caudal putamen being still the most severely affected region. The absolute decline is equal between the striatal subregions. This suggests that the decline of dopamine function starts from the dorsocaudal putamen, but once started, the rate of progression is equal between the subregions of the striatum. In contrast to the striatal decline, the increased cortical F-dopa uptake prevails at least during the first years of PD.

Long-term assessment of striatal dopamine transporters in parkinsonian patients with intrastriatal embryonic mesencephalic grafts

Single-photon emission computed tomography (SPECT) of striatal dopamine transporters (DAT) has been used to demonstrate presynaptic dopaminergic dysfunction and to monitor the progression of Parkinson's disease. In parkinsonian patients who were implanted with embryonic mesencephalic tissue in the striatum, positron emission tomography (PET) has shown an increase in striatal [(18)F]dopa uptake as an indicator of graft survival and striatal reinnervation. The aim of this study was to investigate two patients who had undergone bilateral intrastriatal transplantation of human embryonic mesencephalic tissue using SPECT and the (123)I-labelled DAT ligand N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane (IPT). Two patients were subjected to [(123)I]IPT SPECT according to a standardised protocol prospectively and repeatedly up to 8 years after transplantation. From baseline to year 3 after transplantation, mean striatal DAT availability increased by a mean of 61% (93% and 29% in patients 1 and 2, respectively). It then remained relatively stable up to 8 years in patient 2, but increased further by another 77% of baseline values in patient 1. Clinically, both patients experienced a moderate improvement in motor performance but developed moderate (patient 2) to severe (patient 1) off-medication dyskinesias. Our data indicate that DAT imaging using IPT and SPECT can be used to demonstrate graft survival following dopaminergic tissue implantation. Because SPECT with DAT ligands is widely available in the routine clinical setting, this methodology may be a useful alternative to [(18)F]dopa PET for repeated scanning of grafted parkinsonian patients. The relevance of the long-term increase in DAT binding for the development of off-medication dyskinesias remains to be elucidated further.

Reduced cerebral DOPA uptake in adult patients suffering from phenylketonuria

Reduced cerebral DOPA uptake in adult patients suffering from phenylketonuria

Noninvasive Diagnosis of Focal Hyperinsulinism of Infancy With [18F]-DOPA Positron Emission Tomography

Congenital hyperinsulinism of infancy (CHI) is characterized by severe hypoglycemia due to dysregulated insulin secretion, associated with either focal or diffuse pathology of the endocrine pancreas. The focal condition is caused by a paternally inherited mutation in one of the genes encoding the subunits of the beta-cell ATP-sensitive potassium channel (SUR1/ABCC8 or Kir6.2/KCNJ11) and somatic loss of maternal 11p15 alleles within the affected area. Until now, preoperative diagnostics have relied on technically demanding and invasive catheterization techniques. We evaluated the utility of fluorine-18 l-3,4-dihydroxyphenylalanine ([(18)F]-DOPA) positron emission tomography (PET) to identify focal pancreatic lesions in 14 CHI patients, 11 of which carried mutations in the ABCC8 gene (age 1-42 months). To reduce bias in PET image interpretation, quantitative means for evaluation of pancreatic [(18)F]-DOPA uptake were established. Five patients had a visually apparent focal accumulation of [(18)F]-DOPA and standardized uptake value (SUV) >50% higher (mean 1.8-fold) than the maximum SUV of the unaffected part of the pancreas. When these patients were operated on, a focus of 4-5 x 5-8 mm matching with the PET scan was found, and all were normoglycemic after resection of the focus. The remaining nine patients had diffuse accumulation of [(18)F]-DOPA in the pancreas (SUV ratio <1.5). Diffuse histology was verified in four of these, and pancreatic catheterization was consistent with diffuse pathology in four cases. In conclusion, [(18)F]-DOPA PET is a promising noninvasive method for the identification and localization of the focal form of CHI.

In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease

Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder associated with akinesia, tremor and rigidity. While the characteristic Lewy body pathology targets pigmented and other brainstem nuclei at post-mortem, activated microglia are found in both subcortical and cortical areas. [11C](R)-PK11195 is a positron emission tomography (PET) marker of peripheral benzodiazepine sites (PBBS), which are selectively expressed by activated microglia. We examined 18 PD patients clinically and with [11C](R)-PK11195 and [18F]-dopa PET. Compared to 11 normal controls, the PD patients showed significantly increased mean levels of [11C](R)-PK11195 binding in the pons, basal ganglia and frontal and temporal cortical regions. Eight PD patients were examined longitudinally, and their [11C](R)-PK11195 signal remained stable over 2 years. Levels of microglial activation did not correlate with clinical severity or putamen [18F]-dopa uptake. Our in vivo findings confirm that widespread microglial activation is associated with the pathological process in PD. The absence of significant longitudinal changes suggests that microglia are activated early in the disease process, and levels then remain relatively static, possibly driving the disease via cytokine release.

Novel 2(3H)-Benzothiazolones as Highly Potent and Selective Sigma-1 Receptor Ligands

In an effort to produce a new pharmacological probe with high affinity and selectivity for the sigma-1 receptor, we have synthesized a series of original 2(3H)-benzothiazolones utilizing compound 4 [3-(1-piperidinoethyl)-6-propylbenzothiazolin-2-one] as a lead. Receptor binding affinities were determined at sigma-1 and sigma-2 receptors. The best ligand (9, sigma-1 K-i = 0.56 nM, selectivity ratio > 1000) was obtained with an azepine side-chain. When tested on a wide battery of receptors, including 5HT(2A)(h), 5HT(3)(h), alpha(1), alpha(2), beta(1), beta(2), H-1, H-2, opioids, D-1(h), D-2(h), 5HT uptake, and DOPA uptake, compound 9 showed submicromolar affinity only for alpha(2) (Ki = 205 nM) and H-1 (K-i = 311 nM).

Striatal and cortical pre- and postsynaptic dopaminergic dysfunction in sporadic parkin-linked parkinsonism.

To investigate striatal and cortical pre- and postsynaptic dopaminergic function in parkin-linked parkinsonism, 13 unrelated patients homozygous or compound heterozygous for parkin mutations were studied with [(18)F]dopa and [(11)C]raclopride (RAC) PET. Data were compared with a young-onset Parkinson's disease (YOPD) cohort, matched for age, disease severity and duration, but negative for parkin mutations. Significant changes in [(18)F]dopa uptake and RAC binding potential (BP) were localized in striatum using regions of interest (ROIs) and throughout the entire brain volume with statistical parametric mapping (SPM). As expected, both YOPD and parkin patients showed significant decreases in striatal [(18)F]dopa uptake; however, in parkin patients, additional reductions in caudate and midbrain were localized with SPM. The RAC-BP was significantly decreased in striatal, thalamic and cortical areas (temporal, orbito-frontal and parietal cortex) in parkin compared with YOPD patients. Our [(18)F]dopa PET findings suggest that, compared with YOPD, parkin disease is associated with more severe and widespread presynaptic dopaminergic deficits. The global decreases in D2 binding found in parkin compared with YOPD patients could be a direct consequence of the parkin genetic defect itself or a greater susceptibility to receptor downregulation following long-term dopaminergic agent exposure. Cortical reductions in D2 binding may contribute to the behavioural problems reported in parkin patients.

Decreased availability of intestinal dopamine in transmural colitis may relate to inhibitory effects of interferon-gamma upon L-DOPA uptake.

The present study aimed to evaluate the relationship between intestinal inflammation, interferon-gamma (IFN-gamma) levels and intestinal levels of dopamine, its precursor l-3,4-dihydroxyphenylalanine (L-DOPA), and the activity of aromatic L-amino acid decarboxylase (AADC) activity along the digestive tract in a rat experimental model of colitis. Colitis was induced by rectal administration of 2,4,6-trinitrobenzene sulphonic acid (TNBS). Catechol derivatives were assayed by means of HPLC-EC. It is shown that dopamine and noradrenaline levels in the distal colon (inflamed mucosa), but not in the ileum (non-inflamed mucosa), of TNBS-treated rats were markedly lower than in control animals. A slight decrease in L-DOPA tissue levels, no changes in AADC activity and an increase in plasma IFN-gamma levels accompanied this decrease in dopamine levels. Exposure of Caco-2 cells, a human intestinal epithelial cell line, to human IFN-gamma resulted in a concentration-dependent and long-lasting inhibition of L-DOPA uptake, which most likely explains the decrease in dopamine levels in the inflamed mucosa. Changes in tissue levels of noradrenaline and dopamine in experimental colitis in the rat follow a similar pattern to that observed in patients with Crohn's disease and ulcerative colitis. In this model of experimental colitis, the decrease in dopamine levels is most likely explained by the inhibitory effect of IFN-gamma on L-DOPA uptake by intestinal epithelial cells.

VMAT2 binding is elevated in dopa‐responsive dystonia: Visualizing empty vesicles by PET

Dopa-responsive dystonia (DRD) is a lifelong disorder in which dopamine deficiency is not associated with neuronal loss and therefore it is an ideal human model for investigating the compensatory changes that occur in response to this biochemical abnormality. Using positron emission tomography (PET), we examined the (+/-)-alpha-[(11)C]dihydrotetrabenazine ([(11)C]DTBZ) binding potential of untreated DRD patients and normal controls. Two other PET markers of presynaptic nigrostriatal function, d-threo-[(11)C]methylphenidate ([(11)C]MP) and 6-[(18)F]fluoro-L-dopa ([(18)F]-dopa), and [(11)C]raclopride were also used in the study. We found increased [(11)C]DTBZ binding potential in the striatum of DRD patients. By contrast, no significant changes were detected in either [(11)C]MP binding potential or [(18)F]-dopa uptake rate constant. In addition, we found evidence for increased dopamine turnover in one DRD patient by examining changes in [(11)C]raclopride binding potential in relation to levodopa treatment. We propose that the increase in [(11)C]DTBZ binding likely reflects the dramatic decrease in the intravesicular concentration of dopamine that occurs in DRD; upregulation of vesicular monoamine transporter type 2 (VMAT2) expression may also contribute. Our findings suggest that the striatal expression of VMAT2 (as estimated by [(11)C]DTBZ binding) is not coregulated with dopamine synthesis. This is in keeping with a role for VMAT2 in other cellular processes (i.e., sequestration and release from the cell of potential toxic products), in addition to its importance for the quantal release of monoamines.

Age and severity of nigrostriatal damage at onset of Parkinson's disease

The clinical evolution of Parkinson's disease (PD) is known to be partly dependent on the age of onset. For example, motor complications associated with chronic dopaminomimetic treatment occur more often in younger patients. However, few attempts have been made to characterize the functional pathological differences underlying this age effect. We investigated the relationship between age and severity of nigrostriatal damage at onset of PD. Twenty patients with early PD (symptom duration <or=5 years) with onset before age 50 (n = 10) and with onset after age 50 (n = 10) were studied. The two groups were compared with respect to severity of nigrostriatal damage as evaluated by positron emission tomography (PET) scanning with 6-[(18)F]fluoro-L-dopa ([(18)F]-dopa), (+/-)-alpha-[(11)C]dihydrotetrabenazine ([(11)C]DTBZ), and d-threo-[(11)C]methylphenidate ([(11)C]MP). We found no significant differences between younger- and older-onset PD patients with regard to any of the three presynaptic markers. For putamen, the P-values corresponding to the different PET measurements ranged from P = 0.34 ([(18)F]-dopa) to P = 0.79 ([(11)C]DTBZ). However, after adjusting for treatment and PD duration, regression analysis showed that [(18)F]-dopa uptake correlated positively with age of onset (r = 0.59; P = 0.010). No correlation was found between [(11)C]DTBZ and [(11)C]MP binding potentials and age of onset (P = 0.26 and P = 0.90, respectively). These data suggest that age-of-onset-dependent differences in clinical evolution are not likely to reflect early differences in nigrostriatal pathology in PD. Age-related differences in [(18)F]-dopa uptake may be related to changes in dopamine turnover.

Progression of nigrostriatal dysfunction in a parkin kindred: an [18F]dopa PET and clinical study.

Molecular and clinical characterization of parkin-associated parkinsonism is well described; however, there are no data available on progression of dopamine terminal dysfunction in parkin-associated disease. We have used [(18)F]dopa PET serially to study members of a family with young-onset parkinsonism who are compound heterozygous for mutations in the parkin gene, having an exonic deletion and a novel intronic splice site mutation. Four patients have been studied twice, 10 years apart, to assess disease progression. Additionally, we have studied five asymptomatic family members, four of whom carry a single parkin mutation and one individual who has a normal genotype. Two of the carriers and the individual with the normal genotype had repeat [(18)F]dopa PET. The group of parkin patients showed a significantly slower loss of putamen [(18)F]dopa uptake (P = 0.0008) compared with a group of idiopathic Parkinson's disease (IPD) patients who had baseline putamen [(18)F]dopa uptake and disease severity similar to the parkin group. These results indicate that disease progression in patients with parkin mutations is slower than that of IPD patients. The group of asymptomatic parkin carriers also showed significant striatal dopaminergic dysfunction, and three of them developed subtle extrapyramidal signs. However, the two carriers scanned twice showed no progression over a 7-year period. The slower rate of disease progression in parkin patients may explain the near normal longevity of these patients with young onset parkinsonism.

Echogenicity of the Substantia Nigra

Patients with Parkinson disease characteristically exhibit an increased echogenicity of the substantia nigra (SN) on transcranial sonography, a new neuroimaging technique. The same echo feature of the SN can be identified in 9% of healthy adults. To evaluate the relevance of the echogenic SN in healthy adults. In the first part of the study, 10 healthy subjects younger than 40 years with a distinct SN hyperechogenicity underwent extensive neurological, motor, neuropsychological, and fluorine 18-dopa positron emission tomographic ([18F]-dopa PET) examinations. Results were compared with those of 10 subjects with a low echogenic SN. In the second part of the study, the postmortem brains of 20 patients without extrapyramidal disorders during their lifetime were sonographically examined with a particular focus on SN echogenicity. Subsequently, one half of the brain was prepared for heavy metal analysis, the other for a histological examination. Healthy subjects with SN hyperechogenicity exhibited a significant reduction of the [18F]-dopa uptake, especially in the putamen (Wilcoxon matched pair test: left side, P =.006; right side, P =.009), whereas their neuropsychological and motor performance were normal. Postmortem studies showed that the echogenicity of the SN correlated with its iron content. Increased echogenicity of the SN, characteristically seen in Parkinson disease, is related to a functional impairment of the nigrostriatal system (even in young healthy adults) that can be revealed by [18F]-dopa PET studies. Substantia nigra hyperechogenicity is related to a higher tissue iron level, which is known to enhance the cells' generation of reactive oxygen specimens. Therefore, we hypothesize that transcranial sonography may identify a susceptibility marker for the development of nigral injury that can be detected early in life, prior to the onset of Parkinson disease.

PET Study of [18F]6-Fluoro-l-Dopa Uptake in Neuroleptic- and Mood-Stabilizer-Naive First-Episode Nonpsychotic Mania: Effects of Treatment With Divalproex Sodium

Although dopaminergic hyperactivity has been implicated in mania, the precise location in the brain of the abnormality is unclear. This study assessed presynaptic dopamine function in neuroleptic- and mood-stabilizer-naive nonpsychotic first-episode manic patients before and after treatment with divalproex sodium by measuring [(18)F]6-fluoro-L-dopa ([(18)F]DOPA) uptake in the striatum with positron emission tomography (PET). Thirteen patients with DSM-IV bipolar I disorder, manic episode, and 13 healthy comparison subjects underwent [(18)F]DOPA PET scans. Ten of the 13 patients had repeat PET scans 2-6 weeks after beginning treatment with divalproex sodium monotherapy. [(18)F]DOPA uptake rate constants (K(i) values) in the striatum were calculated by using graphical analysis with activity from the occipital cortex as the input function. No significant differences in [(18)F]DOPA uptake rate constants in the striatum were found between the manic patients and the comparison subjects. After treatment with divalproex sodium, [(18)F]DOPA rate constants were significantly reduced in the patients and were lower in the patients than in the comparison subjects. Although presynaptic dopamine function as reflected by [(18)F]DOPA uptake is not altered in mania, presynaptic dopamine function in manic patients was lower after treatment with divalproex sodium.

Role of tyrosine, DOPA and decarboxylase enzymes in the synthesis of monoamines in the brain of the locust

The metabolic transformation of tyrosine (TYR) by the decarboxylase and hydroxylase enzymes was investigated in the central nervous system of the locust, Locusta migratoria. It has been demonstrated that the key amino acids, 3,4-dihydroxyphenylalanine (DOPA), 5-hydroxytryptophan (5HTP) and tyrosine are decarboxylated in all part of central nervous system. DOPA and 5HTP decarboxylase activities show parallel changes in the different ganglia, but the rank order of the activity of TYR decarboxylase is different. Enzyme purification has revealed that the molecular weights of TYR decarboxylase and DOPA/5HTP decarboxylase are 370,000 and 112,000, respectively. The decarboxylation of DOPA by DOPA/5HTP decarboxylase is stimulated, whereas the decarboxylation of DOPA by TYR decarboxylase is inhibited in the presence of the cofactor pyridoxal-5′-phosphate. TYR hydroxylase could not be detected and 3 H -TYR is found to be metabolised to tyramine (TA), but not to DOPA. The haemolymph contains a significant concentration of DOPA (120 pmol/100 μl haemolymph), and the ganglia incorporates DOPA from the haemolymph by a high affinity uptake process ( K M=12 μM and V max=24 pmol per ganglion/10 min). Our results suggest that no tyrosine hydroxylase is present in the locust CNS and the DOPA uptake into the ganglia by a high affinity uptake process as well as the DOPA decarboxylase enzyme may be responsible for the regulation of the ganglionic dopamine (DA) level. Two types of decarboxylases exist, one of them decarboxylating DOPA and 5HTP (DOPA/5HTP decarboxylase), other decarboxylating TYR (TYR decarboxylase). The DOPA/5HTP decarboxylase enzyme present in the insect brain may correspond to the 5HTP/DOPA decarboxylase in vertebrate brain, whereas TYR decarboxylase is characteristic only for the insect brain.

Echogenicity of substantia nigra determined by transcranial ultrasound correlates with severity of parkinsonian symptoms induced by neuroleptic therapy

Background: Increased echogenicity of the substantia nigra (SN) detected by transcranial sonography is a characteristic ultrasound feature of Parkinson’s disease. This ultrasound feature can also be detected in a subgroup of healthy adults. In recent studies, healthy subjects with this ultrasound feature showed a reduced [ 18F]-Dopa uptake on positron emission tomography (PET), indicating a subclinical alteration of the nigrostriatal system. This study was designed to evaluate whether the severity of neuroleptic side effects is related to the echo-feature of the SN. Methods: In the retrospective part of the study, 93 psychiatric patients with either definite and severe parkinsonism after neuroleptic treatment ( n = 52) or with no or minimal parkinsonian symptoms ( n = 41) were included and underwent transcranial sonography to measure the extension of hyperechogenic areas at the SN. In addition, in the prospective part 11 patients with an acute psychotic episode requiring first-ever neuroleptic treatment underwent ultrasound examination. Subsequently, neuroleptic-induced parkinsonian signs were assessed prospectively. Results: In the retrospective part of the study, patients with severe neuroleptic-induced parkinsonism had more extended echogenic signals at the SN than those with low echogenic SN (U-test; p < .01). The prospective part of the study showed that the severity of parkinsonian symptoms correlated with the echogenicity of the substantia nigra (Spearman’s rank: p < .01). Conclusions: Increased echogenicity of the substantia nigra is associated with impaired function of the nigrostriatal system that can be disclosed by neuroleptic drugs.

Striatal dopaminergic transmission and neocortical glucose utilization in Alzheimer's disease: a triple-tracer positron emission tomography study

The central dopaminergic neuron system is related to cognitive function and behavior. For Alzheimer's disease (AD), using PET and the ligands of dopa, D2 receptor antagonist, and deoxyglucose, we previously found that dopa uptake into the striatum (the Ki value) was correlated with the Mini-Mental State (MMS) score. AD patients exhibiting wandering had an increased level of D2 receptor (the k3/k4 value). The Ki value was correlated with glucose metabolism (CMRglc) of the frontal and temporal lobes, those of wanderers being lower than nonwanderers. We investigated the relationships between the Ki value and the k3/k4 value with reference to cognitive impairment and wandering. Using the three-tracer technique for the single subject, the Ki value, the k3/k4 value, and CMRglc in 12 AD patients were measured. For the wanderers, there was a reverse correlation between the Ki and the k3/k4 values. Multiple regression analysis showed that the score on the verbal fluency test was explained by the Ki value and CMRglc of the frontal and temporal lobes, while MMS score was related to more global areas.