Effect of Repetitive Transcranial Magnetic Stimulation on Long Coronavirus Disease 2019 with Fatigue and Cognitive Dysfunction.

Objectives: There is no established treatment for chronic fatigue and various cognitive dysfunctions (brain fog) caused by long coronavirus disease 2019 (COVID-19). We aimed to clarify the effectiveness of repetitive transcranial magnetic stimulation (rTMS) for treating these symptoms. Methods: High-frequency rTMS was applied to occipital and frontal lobes in 12 patients with chronic fatigue and cognitive dysfunction 3 months after severe acute respiratory syndrome coronavirus 2 infection. Before and after ten sessions of rTMS, Brief Fatigue Inventory (BFI), Apathy Scale (AS), and Wechsler Adult Intelligence Scale-fourth edition (WAIS4) were determined and N-isopropyl-p-[123I]iodoamphetamine single photon emission computed tomography (SPECT) was performed. Results: Twelve subjects completed ten sessions of rTMS without adverse events. The mean age of the subjects was 44.3 ± 10.7 years, and the mean duration of illness was 202.4 ± 114.5 days. BFI, which was 5.7 ± 2.3 before the intervention, decreased significantly to 1.9 ± 1.8 after the intervention. The AS was significantly decreased after the intervention from 19.2 ± 8.7 to 10.3 ± 7.2. All WAIS4 sub-items were significantly improved after rTMS intervention, and the full-scale intelligence quotient increased from 94.6 ± 10.9 to 104.4 ± 13.0. Hypoperfusion in the bilateral occipital and frontal lobes observed on SPECT improved in extent and severity after ten sessions of rTMS. Conclusions: Although we are still in the early stages of exploring the effects of rTMS, the procedure has the potential for use as a new non-invasive treatment for the symptoms of long COVID.

Usefulness of 123I-BMIPP and 201TlCl nuclide scintigraphy in evaluation of myocarditis in patients with polymyositis or dermatomyositis.

ABSTRACT: To investigate the usefulness of 123I-BMIPP/201TlCl scintigraphy for evaluating the presence of myocarditis in patients with polymyositis (PM) or dermatomyositis (DM).We performed a retrospective study of 26 patients diagnosed with new-onset active PM/DM who underwent 123I-BMIPP/201TlCl scintigraphy between 01 April 2010 and 20 March 2015. We determined the 123I-BMIPP/201TlCl ratio and grouped the patients according to presence or absence of a mismatch. We evaluated the relationship between mismatch and the laboratory and echocardiographic findings.Mismatch was found in 13 (50%) patients. There was no statistically significant difference in age, cardiac troponin T, myoglobin, myosin light chain, aldolase levels, E wave/A wave ratio, right ventricular systolic pressure between the mismatch and non-mismatch groups. Left ventricular end-diastolic and end-systolic dimensions were significantly greater in the mismatch group (45.0 vs 42.5 mm, P =  < .01 and 29.5 mm vs 25.0 mm, P < .01). Left ventricular ejection fraction was significantly lower in the mismatch group (63.5% vs 71.5%, P = .04). Significant inverse correlation (r = -0.44, P = .03) was observed between left ventricular ejection fraction and mismatch ratio.The use of 123I-BMIPP/ 201TlCl scintigraphy may be considered for evaluating myocarditis in patients with PM/DM.

Investigation of Cushing's and subclinical Cushing's syndromes using adrenocortical scintigraphy.

OBJECTIVES: This study assessed the factors related to the intake rate of adrenocortical scintigraphy in Cushing's and subclinical Cushing's syndromes, in addition to the methods for differentiating between the two. METHODS: Clinical findings, blood sampling, and adrenocortical scintigraphy collected at St. Marianna University School of Medicine from 1 January 2010 to 31 December 2019 were used to diagnose initial-onset Cushing's syndrome and subclinical Cushing's syndrome, and patients who underwent 131I-NP-59 adrenocortical scintigraphy were used as study subjects. RESULTS: A total of 24 (8 male and 16 female) patients were selected. Of them, 7 had Cushing's syndrome and 17 had subclinical Cushing's syndrome. A correlation coefficient of -0.474 (P = 0.026) was determined between the intake rate after 7 days and adrenocorticotropic hormone levels. Intake rates after 5 days were 0.51% and 0.31% for Cushing's and subclinical Cushing's syndromes, respectively, and were statistically significant (P = 0.03). Intake rates after 7 days were 0.47% and 0.30% for Cushing's and subclinical Cushing's syndromes, respectively, and were statistically significant (P = 0.04). Receiver operating characteristic analysis results of Cushing's and subclinical Cushing's syndromes for intake rates after 7 days were as follows: cutoff value, 0.248; area under curve, 0.769; and 95% confidence interval, 0.561-0.977. CONCLUSION: There were differences in the intake rates of adrenocortical scintigraphy between the Cushing's syndrome group and subclinical Cushing's syndrome group, making it possible to differentiate between the two using the intake rate.

Comparison of diagnostic precision for bone metastasis of primary breast cancer between BONENAVI version 1 and BONENAVI version 2.

OBJECTIVE: The aim of this study was to compare the diagnostic precision of bone scintigraphy with BONENAVI version 1 and BONENAVI version 2 in bone metastasis of primary breast cancer. METHODS: The subjects were 56 consecutive patients (all women, mean age 59 ± 12.7 years) who underwent bone scintigraphy with Tc-MDP and were diagnosed with bone metastasis of primary breast cancer from January 2012 to November 2014. Bone scintigraphy was performed with BONENAVI version 1 and BONENAVI version 2 to calculate artificial neural network (ANN), bone scan index (BSI), and hot-spot values, with ANN ≥ 0.5 considered to reflect bone metastasis for the calculation of sensitivity. Mean ANN, BSI, hot-spot values, and sensitivity were compared between BONENAVI version 1 and BONENAVI version 2, with P < 0.05 considered a significant difference. RESULTS: With BONENAVI version 1, mean ANN was 0.73 ± 0.29, BSI was 1.47 ± 1.85, the hot-spot value was 12.4 ± 12.5, and sensitivity was 76.8% (43/56). With BONENAVI version 2, the mean ANN was 0.86 ± 0.19, BSI was 1.53 ± 2.09, hot-spot value was 12.9 ± 15.6, and sensitivity was 94.6% (53/56). BONENAVI version 2 yielded significantly better ANN and sensitivity than BONENAVI version 1 (both P < 0.01). CONCLUSION: BONENAVI version 2 has improved sensitivity for detecting bone metastasis of primary breast cancer compared to BONENAVI version 1.

Time course of bone metabolism at the residual ridge beneath dentures observed using ¹8F-fluoride positron emission computerized-tomography/computed tomography (PET/CT).

OBJECTIVE: Excessive pressure due to wearing mal-adapting dentures is well known to cause residual bone resorption beneath the denture. X-rays have been commonly utilized to evaluate the changes in the bone beneath the denture. However, X-ray images merely detect bone density and relatively large changes in the bone shape and structure, whereas nuclear medicine imaging can detect functional changes, which occur prior to structural changes. This article aimed to describe the time course of the bone metabolism at the residual ridge beneath the denture following denture use by (18)F-fluoride positron emission computerized-tomography (PET)/computed tomography (CT) scanning. METHODS: Three subjects, who had a free-end edentulous mandible, were treated with a denture replacing the edentulous region of the dental arch. The metabolic changes in the residual bone beneath the denture were assessed by (18)F-fluoride PET/CT imaging. (18)F-fluoride PET/CT scanning was performed at baseline, and 4-6 and 13 weeks after denture use. A volume of interest (VOI) was placed on their mandibles at the edentulous region beneath the denture on the PET/CT image. CT value and mean standardized uptake value (SUV) of the VOI were calculated. The difference in the time variation between the CT value and SUV was analyzed. RESULTS: The adaptation of the denture base to the residual ridge was successful, and there was no trouble such as pain at the residual ridge beneath the denture. The SUVs of each VOI significantly increased at 4-6 weeks after denture use and then decreased at 13 weeks in all three subjects (P < 0.05; two-way ANOVA, Dunnett test). On the other hand, the CT images showed no obvious changes in the bone shape or structure beneath the dentures, and the CT values of each VOI remained static after denture use in all three subjects. CONCLUSIONS: This study indicates that in the present first-time removable partial denture (RPD) users, wearing of a well-adapted RPD initially increased bone metabolism beneath the denture and then decreased it at around 13 weeks after RPD use without any bone structural changes detectable by clinical X-rays. These metabolic changes are a mechanobiological reaction to the pressure induced by RPD use.

Bone metabolism of residual ridge beneath the denture base of an RPD observed using NaF-PET/CT.

PATIENT: A 66-year-old woman, who had a bilateral free-end edentulous mandible and no experience with dentures, was examined for the chief complaint of masticatory dysfunction on left side of dental arch. A unilateral distal extension removable partial denture (RPD) replacing lower-left molars was selected. Tomographic images were obtained using Fluorine-18 NaF positron emission computerized tomography (NaF-PET)/computed tomography (CT) before the RPD use and at 1, 6, and 13 weeks after the RPD use to observe the metabolic changes in residual bone caused by the RPD use. PET standardized uptake values (SUVs) and CT values were calculated for lower-left edentulous site (test side) and lower-right edentulous site (control side). As a result, SUVs on the control side remained static after the RPD use, whereas those on the test side increased at 1 and 6 weeks after the RPD use and then decreased. However, CT images showed no obvious changes in the bone shape and structure beneath RPD, and CT values both on the control and test sides did not change either. DISCUSSION: This report shows that NaF-PET could detect bone metabolic changes soon after the RPD use, which cannot be detected by clinical X-rays. The SUV changes may be a mechanobiological reaction to the pressure due to the RPD use, and wearing of the RPD may increase the bone turnover beneath denture. CONCLUSION: This report demonstrates that wearing of an RPD increases bone turnover beneath denture immediately after the RPD use without clinically detectable changes in bone structure or volume.

Cerebral metabolic changes in men after chiropractic spinal manipulation for neck pain.

BACKGROUND: Chiropractic spinal manipulation (CSM) is an alternative treatment for back pain. The autonomic nervous system is often involved in spinal dysfunction. Although studies on the effects of CSM have been performed, no chiropractic study has examined regional cerebral metabolism using positron emission tomography (PET). OBJECTIVE: The aim of the present study was to investigate the effects of CSM on brain responses in terms of cerebral glucose metabolic changes measured by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: Twelve male volunteers were recruited. Brain PET scanning was performed twice on each participant, at resting and after CSM. Questionnaires were used for subjective evaluations. A visual analogue scale (VAS) was rated by participants before and after chiropractic treatment, and muscle tone and salivary amylase were measured. RESULTS: Increased glucose metabolism was observed in the inferior prefrontal cortex, anterior cingulated cortex, and middle temporal gyrus, and decreased glucose metabolism was found in the cerebellar vermis and visual association cortex, in the treatment condition (P < .001). Comparisons of questionnaires indicated a lower stress level and better quality of life in the treatment condition. A significantly lower VAS was noted after CSM. Cervical muscle tone and salivary amylase were decreased after CSM. Conclusion The results of this study suggest that CSM affects regional cerebral glucose metabolism related to sympathetic relaxation and pain reduction.

Pituitary-adrenal functions in a hereditary hypothyroid (rdw) rat.

The rdw rat is a hereditary hypothyroid strain isolated from Wistar-Imamichi rats. In the present study, adrenocorticotropic hormone (ACTH) and corticosterone responses to restraint stress (120 min) were examined in rdw adult male rats. ACTH response to restraint stress was higher in rdw rats than in hetero control rats. The plasma concentrations of corticosterone were lower in rdw rats than in control rats during the first 30 min after the onset of stress. Both ACTH and corticosterone responses to restraint stress in rdw rats recovered to control levels after thyroxine (T4) replacement therapy. These results suggest that hereditary hypothyroidism causes adrenal dysfunction directly and that hypersecretion of ACTH is a result of reduced corticosterone in rdw rats.

Bone metabolic activity around dental implants under loading observed using bone scintigraphy.

PURPOSE: The purpose of this study was to determine dynamic changes in bone metabolism around osseointegrated titanium implants under mechanical stress. MATERIALS AND METHODS: Two titanium implants were inserted parallel to each other in the tibiae of rats and perpendicular to the bone surface with the superior aspect of the implant exposed. Eight weeks after insertion, closed coil springs with 0.5, 1.0, 2.0, and 4.0 N were applied to the exposed superior portion of the implant for 7 weeks to apply a continuous mechanical stress. Bone scintigrams were performed using a gamma camera with a modified high-resolution pinhole collimator. Images were made at 1, 4, 7, 10, 14, 21, 28, 49, and 56 days after insertion and at 3 days and at weekly intervals until 7 weeks after load application. The ratio of the metabolic activity around the implants to that around a reference site (uptake ratio) was established. The Friedman, Steel, and Tukey tests (P < .05) were used to assess statistical significance. RESULTS: In the process of osseointegration, the uptake ratio increased during the first week after implant insertion and then gradually decreased. During the initial 3 weeks the uptake ratio was significantly higher than at 1 day after insertion. In the process of load application, the uptake ratio increased with 2.0- and 4.0-N loads; it was significantly higher until 6 weeks than it had been before load application. CONCLUSIONS: Bone metabolism around the implants increases with loading and depends on the magnitude and period of the loading.

Muscle activity during a dash shown by 18F-fluorodeoxyglucose positron emission tomography.

BACKGROUND: 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has been used to examine muscle activity during running. The dash is a basic activity in various kinds of sports but differs from running in terms of intensity and severity. The purpose of this study was to evaluate muscle activity during running at full speed using FDG PET. METHODS: Six healthy men were investigated during a dash for 10 min after intravenous injection of FDG (37 MBq). Another six healthy men were studied as controls. PET images were obtained 45 min after the FDG injection. Regions of interest were drawn on the anterior and posterior thighs and the anterior and posterior legs. The standardized uptake value (SUV) was calculated to examine the FDG uptake of muscle tissue per unit volume according to an equation. RESULTS: In the control group, the mean SUVs of the anterior thigh, posterior thigh, anterior leg, and posterior leg were 0.49 +/- 0.04, 0.44 +/- 0.02, 0.46 +/- 0.05, and 0.44 +/- 0.07, respectively. In the dash group, the mean SUVs of the anterior thigh, posterior thigh, anterior leg, and posterior leg were 0.74 +/- 0.20, 0.79 +/- 0.08, 0.61 +/- 0.07, and 0.60 +/- 0.08, respectively. FDG accumulation of every one of the four compartments in the dash group was significantly higher than that in the control. FDG accumulation of the posterior thigh was significantly higher than that of the anterior and the posterior leg in the dash group (P < 0.02). CONCLUSION: Based on the results of our investigation, posterior thigh muscles were especially active during a dash.

Dissociable roles of prefrontal and anterior cingulate cortices in deception.

Recent neuroimaging studies have shown the importance of the prefrontal and anterior cingulate cortices in deception. However, little is known about the role of each of these regions during deception. Using positron emission tomography (PET), we measured brain activation while participants told truths or lies about two types of real-world events: experienced and unexperienced. The imaging data revealed that activity of the dorsolateral, ventrolateral and medial prefrontal cortices was commonly associated with both types of deception (pretending to know and pretending not to know), whereas activity of the anterior cingulate cortex (ACC) was only associated with pretending not to know. Regional cerebral blood flow (rCBF) increase in the ACC was positively correlated with that in the dorsolateral prefrontal cortex only during pretending not to know. These results suggest that the lateral and medial prefrontal cortices have general roles in deception, whereas the ACC contributes specifically to pretending not to know.

Functional brain mapping of actual car-driving using [18F]FDG-PET.

AIMS: This study aims at identifying the brain activation during actual car-driving on the road, and at comparing the results to those of previous studies on simulated car-driving. METHODS: Thirty normal volunteers, aged 20 to 56 years, were divided into three subgroups, active driving, passive driving and control groups, for examination by positron emission tomography (PET) and [18F]2-deoxy-2-fluoro-D-glucose (FDG). The active driving subjects (n = 10) drove for 30 minutes on quiet normal roads with a few traffic signals. The passive driving subjects (n = 10) participated as passengers on the front seat. The control subjects (n = 10) remained seated in a lit room with their eyes open. Voxel-based t-statistics were applied using SPM2 to search brain activation among the subgroups mentioned above. RESULTS: Significant brain activation was detected during active driving in the primary and secondary visual cortices, primary sensorimotor areas, premotor area, parietal association area, cingulate gyrus, the parahippocampal gyrus as well as in thalamus and cerebellum. The passive driving manifested a similar-looking activation pattern, lacking activations in the premotor area, cingulate and parahippocampal gyri and thalamus. Direct comparison of the active and passive driving conditions revealed activation in the cerebellum. CONCLUSION: The result of actual driving looked similar to that of simulated driving, suggesting that visual perception and visuomotor coordination were the main brain functions while driving. In terms of attention and autonomic arousal, however, it seems there was a significant difference between simulated and actual driving possibly due to risk of accidents. Autonomic and emotional aspects of driving should be studied using an actual driving study-design.

Perforin-dependent cell death in skin allograft rejection of the terrestrial slug Incilaria fruhstorferi.

The rejection of allografts in mammals is mainly mediated by cytotoxic T-lymphocytes, whereas no comparable immunoreactive cells have been described in invertebrates. The present study was undertaken to determine whether similar cytotoxic effector cells are present when allograft rejection occurs in the terrestrial slug Incilaria fruhstorferi. A piece of dorsal skin from a donor animal was orthotopically transplanted to a recipient. Immunohistochemistry for perforin, detection of apoptosis by the TUNEL (TdT-mediated dUTP-biotin nick-end labeling) method, and electron microscopy were performed using both donor and recipient tissues. Cellular changes in the rejection process continued over for 40 days. Two functional types of "effector" cells were recognized at the rejection site, but they were observed to be macrophages possessing perforin granules and phagocytosing damaged cells of the allograft. Three days after transplantation, the perforin-positive cells were recognized only in the recipient tissue surrounding the allograft. Five days after transplantation, these cells started to appear in the graft, while they disappeared from the host tissue. However, TUNEL-positive cells were not observed throughout the graft-rejection process. Electron microscopic examination of the graft tissue revealed autophagic degeneration of epithelial cells, mucous cells, pigment cells, fibroblasts, and muscle cells. These observations suggest that the molluscan slug has the capability to recognize differences in cell-surface molecules between the allogeneic and recipient tissues, and that an allograft is chronically rejected due to a type of immunocyte that can induce perforin-dependent cell death.

Attenuation of fluctuating striatal synaptic dopamine levels in patients with Parkinson disease in response to subthalamic nucleus stimulation: a positron emission tomography study.

OBJECT: The "wearing-off" phenomenon often hampers the treatment of Parkinson disease (PD). Although deep brain stimulation (DBS) of the subthalamic nucleus (STN) is known to ameliorate the wearing-off phenomenon, the mechanism by which it does this remains unclear. As part of an inquiry into the mechanism of STN DBS, the authors measured synaptic dopamine levels in the striatum by performing positron emission tomography (PET) with [11C]raclopride. METHODS: Three patients with PD who were experiencing the wearing-off phenomenon underwent PET scanning before and after DBS of the STN. The clinical features in these patients were evaluated by applying the Hoehn and Yahr, United Parkinson's Disease Rating, and Schwab and England Activities of Daily Living Scales. Before and after surgery, PET scans were obtained using [11C]raclopride prior to and 1 hour following an oral administration of levodopa. Regions of interest for the [11C]raclopride binding potential (RacloBP) were set in the bilateral putamen and the caudate nucleus. All clinical scores were dramatically improved postoperatively. Deep brain stimulation of the STN reduced the baseline RacloBP in both the putamen and caudate nucleus, but the differences between the pre- and postoperative levels were insignificant. Before DBS of the STN, the levodopa administration significantly reduced RacloBP in the putamen (p < 0.0001). Postoperatively the drug-induced reduction in RacloBP became statistically insignificant. The drug-induced increase in synaptic dopamine concentrations in the putamen preoperatively was estimated to be approximately four times higher than that after surgery (p < 0.01). The drug-induced RacloBP change in the caudate nucleus was similar to that in the putamen, although the magnitude of the change was lower (p < 0.005). The drug-induced increase in the caudate nucleus was also reduced postoperatively (p < 0.05). CONCLUSIONS: Deep brain stimulation of the STN induces the stabilization of synaptic dopamine concentrations in the striatum and may attribute to the alleviation of levodopa-related motor fluctuations.

An experimental study on O-[18F]fluoromethyl-L-tyrosine for differentiation between tumor and inflammatory tissues.

OBJECTIVE: O-[18F]fluoromethyl-L-tyrosine (18F-FMT) is a recently developed tumor-detecting agent with simple preparation and high radiochemical yields. The aim of this study was to assess the potency of 18F-FMT for differentiating tumor and inflammatory tissues using an animal model with an implanted tumor and experimentally induced inflammatory foci. METHODS: An ascites hepatoma cell line, AH109A, turpentine oil and Staphylococcus aureus were inoculated subcutaneously into Donryu rats as a tumor model, aseptic inflammation model and bacterial infection model, respectively. The biodistribution of radioactivity was assessed in rats at 5, 10, 30, 60, and 120 min after injection with 18F-FMT. Dual tracer whole-body and macro autoradiographies were performed 60 min after injection with a mixture of 18F-FMT and 2-deoxy-D-[1-14C]glucose (14C-DG). RESULTS: Tumor uptake of 18F-FMT was on average 1.27% injected dose per gram of tissue (%ID/g) and 1.43% ID/g at 30 min and 60 min, respectively and significantly higher than that in other normal tissues, except the pancreas (3.48% ID/g at 60 min). The uptakes in the aseptic and bacterial inflammatory tissues were very low and were not different from those of the background tissues. Dual tracer whole-body and macro autoradiographic studies showed that tumor uptake of 18F-FMT was clearly higher than uptake by the other tissues, while 18F-FMT accumulated much less both in aseptic and bacterial inflammatory tissues. In contrast, the 14C-DG images showed high accumulations not only in tumors but also in aseptic and bacterial inflammatory tissues. CONCLUSION: 18F-FMT seems to be a promissing tracer for the differentiation between tumor and inflammation because of higher specificity to tumor.

Recruitment of fusiform face area associated with listening to degraded speech sounds in auditory-visual speech perception: a PET study.

For the fast and accurate cognition of external information, the human brain seems to integrate information from multi-sensory modalities. We used positron emission tomography (PET) to identify the brain areas related to auditory-visual speech perception. We measured the regional cerebral blood flow (rCBF) of young, normal volunteers during the presentation of dynamic facial movement at vocalization and during a visual control condition (visual noise), both under the two different auditory conditions of normal and degraded speech sounds. The subjects were instructed to listen carefully to the presented speech sound while keeping their eyes open and to say what they heard. The PET data showed that elevation of rCBF in the right fusiform gyrus (known as the "face area") was not significant when the subjects listened to normal speech sound accompanied by a dynamic image of the speaker's face, but was significant when degraded speech sound (filtered with a 500 Hz low-pass filter) was presented with the facial image. The results of the present study confirm the possible involvement of the fusiform face area (FFA) in auditory-visual speech perception, especially when auditory information is degraded, and suggest that visual information is interactively recruited to make up for insufficient auditory information.

The neural correlates of driving performance identified using positron emission tomography.

Driving is a complex behavior involving multiple cognitive domains. To identify neural correlates of driving performance, [15O]H2O positron emission tomography was performed using a simulated driving task. Compared with the resting condition, simulated driving increased regional cerebral blood flow (rCBF) in the cerebellum, occipital, and parietal cortices. Correlations between rCBF and measurements of driving performance were evaluated during simulated driving. Interestingly, rCBF in the thalamus, midbrain, and cerebellum were positively correlated with time required to complete the course and rCBF in the posterior cingulate gyrus was positively correlated with number of crashes during the task. These brain regions may thus play roles in the maintenance of driving performance.

Risperidone is effective for wandering and disturbed sleep/wake patterns in Alzheimer's disease.

Behavioral and psychological symptoms of dementia (BPSD), especially aggressiveness, wandering, and sleep disturbance, are a major burden for caregivers. Daily sleep/wake patterns and wandering of institutionalized patients with Alzheimer's disease (AD) were visually monitored, and 34 patients who manifested wandering were selected and randomly classified into 2 groups: the risperidone group and the nonrisperidone group. After an administration of low-dose risperidone for the risperidone group, the BPSD were reassessed. The binding potentials of dopamine D2 receptor for preadministration and postadministration of risperidone were assessed using positron emission tomography (PET) for 1 case. After the use of risperidone, aggressiveness and wandering were reduced and the nighttime sleeping hours were increased. The PET revealed that the binding potential of dopamine receptor was increased after administration of the drug, associated with improved sleep/wake patterns and behavioral abnormality. Possible serotonergic modulation of dopaminergic function might explain the neurobiological basis of the effect of risperidone.

The role of sigma-receptors in levodopa-induced dyskinesia in patients with advanced Parkinson disease: a positron emission tomography study.

OBJECT: Levodopa-induced dyskinesia (LID) in patients with Parkinson disease (PD) mimics acute dystonic reactions induced by antipsychotic agents, possibly mediated by sigma-receptors; however, there are few reports in which the relationship between sigma-receptors and LID in advanced PD is investigated. The binding potential of cerebellar sigma-receptors before and after a pallidal surgery for dyskinesia in patients with advanced PD is assessed. METHODS: Six patients with advanced PD (male/female ratio 3:3, age 56.7 +/- 9.8 years) underwent stereotactic pallidal surgery (two posteroventral pallidotomy procedures and four deep brain stimulation of the globus pallidus internus, including one bilateral case). Clinical features of patients with PD were assessed using Hoehn and Yahr (H & Y) stages, the Unified Parkinson's Disease Rating Scale (UPDRS), and the Schwab and England Activities of Daily Life Scale (S & E). The LID was evaluated by LID severity score. The binding potential of cerebellar sigma-receptors was determined before and after the surgery by 11C-nemonapride positron emission tomoraphy, a specific radioligand for sigma-receptors in the cerebellum. All clinical scores, especially the LID severity score, were dramatically improved after the surgery (p < 0.05). Preoperatively, contralateral cerebellar binding potential was significantly elevated (p < 0.01), and it was reduced after the surgery, but it was still higher than that of healthy volunteers (p < 0.05). The ipsilateral cerebellar binding potential remained unchanged after the surgery. The level of binding potential did not correlate with H & Y stage, UPDRS, or S & E score, but a strong positive correlation was seen between the binding potential and the preoperative LID severity score when the patients were receiving medication (r = 0.893, p < 0.05). CONCLUSIONS: Cerebellar sigma-receptors may potentially involve the genesis of LID in advanced PD.