Comparative analysis of sleep parameters and structures derived from wearable flexible electrode sleep patches and polysomnography in young adults.

Polysomnography (PSG) is the gold standard for clinical sleep monitoring, but its cost, discomfort, and limited suitability for continuous use present challenges. The flexible electrode sleep patch (FESP) emerges as an economically viable and patient-friendly solution, offering lightweight, simple operation, and self-applicable. Nevertheless, its utilization in young individuals remains uncertain. The objective of this study was to compare sleep data obtained by FESP and PSG in healthy young individuals and analyze agreement for sleep parameters and structure classification. Overnight monitoring with FESP and PSG recordings in 48 participants (mean age: 23 yr) was done. Correlation analysis, Bland-Altman plots, and Cohen's kappa coefficient assessed consistency. Sensitivity, specificity, and predictive values compared classification against PSG. FESP showed strong correlation and consistency with PSG for sleep monitoring. Bland-Altman plots indicated small errors and high consistency. Kappa values (0.70-0.84) suggested substantial agreement for sleep stage classification. Pearson correlation coefficient values for sleep stages (0.75-0.88) and sleep parameters (0.80-0.96) confirm that FESP has a strong application. Intraclass correlation coefficient yielded values between 0.65 and 0.97. In addition, FESP demonstrated an impressive accuracy range of 84.12-93.47% for sleep stage classification. The FESP also features a wearable self-test program with an error rate of no more than 8% for both deep sleep and wake. In young adults, FESP demonstrated reliable monitoring capabilities comparable to PSG. With its low cost and user-friendly design, FESP is a potential alternative for portable sleep assessment in clinical and research applications. Further studies involving larger populations are needed to validate its diagnostic potential.NEW & NOTEWORTHY By comparison with PSG, this study confirmed the reliability of an efficient, objective, low-cost, and noninvasive portable automatic sleep-monitoring device FESP, which provides effective information for long-term family sleep disorder diagnosis and sleep quality monitoring.

Impulsive and compulsive reading comprehension in the prison population.

BACKGROUND: Developmental dyslexia is characterized by reading and writing deficits that persist into adulthood. Dyslexia is strongly associated with academic underachievement, as well as impulsive, compulsive, and criminal behaviors. The aims of this study were to investigate impulsive or compulsive reading comprehension, analyzing the differences in reading errors between two distinct groups -one with Antisocial Personality Disorder (ASPD) and another with Obsessive-Compulsive Personality Disorder (OCPD) and examine their correlation with criminal behavior within a prison population. METHODS: We gathered data from 194 participants: 81 with ASPD and 113 with OCPD from a prison center. Participants took part in interviews to gather data on demographic, criminal, and behavioral data. Additionally, the participants underwent various assessments, including the International Examination for Personality Disorders; Symptom Inventory, and Battery for the Assessment of Reading Processes in Secondary and High School - Revised. RESULTS: Our analysis revealed differences in reading skills between the ASPD and OCPD groups. Specifically, the OCPD group showed poorer performance on lexical selection, semantic categorization, grammar structures, grammatical judgements, and expository comprehension when compared with the ASPD group. Conversely, the OCPD group obtained higher scores on narrative comprehension relative to the ASPD group. CONCLUSIONS: The OCPD group showed slow lexical-phonological coding and phonological activation.

2D:4D-ratios among individuals with amphetamine use disorder, antisocial personality disorder and with both amphetamine use disorder and antisocial personality disorder.

BACKGROUND: There is sufficient evidence that the index-finger-to-ring-finger-ratio (2D:4D-ratio) is associated with testosterone and estrogen exposure during the fetal stage. More specifically, a lower 2D:4D-ratio (that is; a shorter index finger, compared to a longer ring finger) was associated with a prenatally higher testosterone and lower estrogen exposure during the first trimester of the fetal stage. At a behavioral level, among adults, a lower 2D:4D-ratio was associated with a higher competitive performance among both female and male professional athletes, and with personality traits such as higher scores for mental toughness, dark triad traits, and aggressive behavior, and internet use disorder. Here, we tested, if 2D:4D-ratios differed among three clinical samples of individuals with amphetamine use disorder (AUD), antisocial personality disorder (ASPD), or both AUD and ASPD (AUD + ASPD), and when compared to healthy controls. METHOD: The sample consisted of 44 individuals (mean age: 32.95 years; 22.7% females) diagnosed either with AUD (n = 25), ASPD (n = 10) or both AUD + ASPD (n = 9), and of 36 healthy controls (mean age: 23.28; 25% females). After a thorough clinical assessment, participants provided the scans of their right-hand palm to measure the lengths of their index finger and ring finger. Further, participants with AUD, ASPD and both AUD + ASPD completed a series of self-rating questionnaires on Dark Triad traits, narcissism sensitivity, and intolerance of uncertainty. RESULTS: Compared to healthy controls, participants with AUD, ASPD, or AUD + ASPD showed statistically significantly lower 2D:4D-ratios. Participants with AUD + ASPD showed statistically significantly lowest 2D:4D-ratios, compared to participants with AUD and compared to healthy controls. For the clinical sample, a lower 2D:4D-ratio was associated with higher Dark Triad traits. 2D:4D-ratios were unrelated to narcissism sensitivity or intolerance of uncertainty. Higher scores for Dark Triad traits were associated with higher scores for narcissism sensitivity and intolerance of uncertainty. CONCLUSIONS: Compared to healthy controls, individuals with amphetamine use disorder and concomitant antisocial personality disorder (AUD + ASPD) appeared to have been exposed to particularly high prenatal testosterone and particularly low estrogen concentrations, which, at a behavioral level, might have led to a fast life history for immediate resource acquisition.

Substance Use Disorders and Antisocial Personality Disorder among a Sample of Incarcerated Individuals with Inadequate Health Care: Implications for Correctional Mental-Behavioural Health and Addiction Services.

Epidemiological estimates of substance use disorders (SUD) are critical for the planning of evidence-informed intervention and services. In this study, 250 incarcerated individuals in Nigeria were interviewed with the Mini International Neuropsychiatric Inventory (MINI) to diagnose SUD and antisocial personality disorder (ASPD). Most of the participants were males (97.6%), and the mean age was 35.4 (SD=13.5) years. Substance use disorder and ASPD were prevalent in 57.6% and 11.2% of the participants, respectively. Of those diagnosed with SUD, 35.2% and 22.4% had poly-SUD and mono-SUD respectively. Psychotic and dependence syndromes involving cannabis misuse were the most prevalent poly-SUD, and mono-SUD was characterized by alcohol, nicotine, and opioid dependence syndromes. Substance use disorder was more likely in participants charged with robbery and convicted, while ASPD was associated with prior and long-term imprisonment. There is a need for effective integration of treatment for ASPD/SUD into correctional mental health services in settings with inadequate health care using an appropriate model and a viable strategy.

Formation of N-acyl-phosphatidylethanolamines by cytosolic phospholipase A2ε in an ex vivo murine model of brain ischemia.

N-Acyl-phosphatidylethanolamines (NAPEs), a minor class of membrane glycerophospholipids, accumulate along with their bioactive metabolites, N-acylethanolamines (NAEs) during ischemia. NAPEs can be formed through N-acylation of phosphatidylethanolamine by cytosolic phospholipase A2ε (cPLA2ε, also known as PLA2G4E) or members of the phospholipase A and acyltransferase (PLAAT) family. However, the enzyme responsible for the NAPE production in brain ischemia has not yet been clarified. Here, we investigated a possible role of cPLA2ε using cPLA2ε-deficient (Pla2g4e-/-) mice. As analyzed with brain homogenates of wild-type mice, the age dependency of Ca2+-dependent NAPE-forming activity showed a bell-shape pattern being the highest at the first week of postnatal life, and the activity was completely abolished in Pla2g4e-/- mice. However, liquid chromatography-tandem mass spectrometry revealed that the NAPE levels of normal brain were similar between wild-type and Pla2g4e-/- mice. In contrast, post-mortal accumulations of NAPEs and most species of NAEs were only observed in decapitated brains of wild-type mice. These results suggested that cPLA2ε is responsible for Ca2+-dependent formation of NAPEs in the brain as well as the accumulation of NAPEs and NAEs during ischemia, while other enzyme(s) appeared to be involved in the maintenance of basal NAPE levels.

Increased ghrelin and decreased leptin levels in patients with antisocial personality disorder.

OBJECTIVE: The study aimed to compare acyl ghrelin (AG), des-acyl ghrelin (DAG), and leptin levels considered to be used as biological markers in the etiopathogenesis of antisocial personality disorder (ASPD) with healthy controls, and to investigate the relationship between these hormones and aggression and impulsivity. METHOD: The study included 45 patients with ASPD and 61 healthy people in the control group. Sociodemographic data form, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Barratt Impulsiveness Scale (BIS-11), and Buss-Durkee Aggression Scale (BDAS) were applied to all participants. Fasting venous blood samples were taken from all participants at the same time of the day and the height and weight of the participants were measured. RESULTS: It was found that the mean serum AG and DAG levels were significantly higher than that of healthy controls whereas leptin hormone levels were significantly lower in patients compared to healthy controls. BDI, BAI, BIS-11, and BDAS scores of the patients were significantly higher compared to healthy controls. There was a positive correlation between AG and DAG hormone levels and impulsivity and aggression. DISCUSSION: The present study is the first in the literature to examine AG, DAG, and leptin hormone levels of patients diagnosed with ASPD. According to the results of the study, it is believed that changes in serum leptin and ghrelin levels will bring a new perspective in terms of understanding the pathophysiological mechanism of ASPD. Further studies are required to explain the definitive roles of these hormones in ASPD.

Surviving Senior Psychopathy: Informant Reports of Deceit and Antisocial Behavior in Multiple Types of Relationships.

A prevailing view among researchers and mental health clinicians is that symptoms of antisocial personality disorder (ASPD)/psychopathy decrease as affected individuals reach middle age. In the current investigation, informants were surveyed about the behavior of individuals who they believed showed traits of ASPD/psychopathy and were over the age of 50. A final sample of 1,215 respondents rated the index individuals according to the ASPD/psychopathy traits derived from the pre-publication first draft of the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition, revealing high endorsement of traits associated with ASPD. Survey respondents reported their observations that individuals who met a threshold for putative ASPD/psychopathy continued to engage in antisocial behavior after age 50, and as a result the respondents endured significant harm, including material losses, financial losses, and various self-reported mental health problems. Those who knew the index individuals both before and after the age of 50 were specifically asked whether there was a change in the individual's engagement in manipulation, deceit, and antisocial behavior; 93% of respondents reported that the behavior was just as bad or worse after age 50. Other researchers have suggested that the DSM diagnostic criteria do not accurately describe ASPD/psychopathy symptoms and behavior in older adults, and that the disorder remains stable, but its manifestation changes with age. This study supports those conclusions.

Quantitative analysis of fluorescent ligand binding to dopamine D3 receptors using live-cell microscopy.

Dopamine receptors are G protein-coupled receptors that have several essential functions in the central nervous system. A better understanding of the regulatory mechanisms of ligand binding to the receptor may open new possibilities to affect the downstream signal transduction pathways. The majority of the available ligand binding assays use either membrane preparations, cell suspensions, or genetically modified receptors, which may give at least partially incorrect understanding of ligand binding. In this study, we implemented an assay combining fluorescence and bright-field microscopy to measure ligand binding to dopamine D3 receptors in live mammalian cells. For membrane fluorescence intensity quantification from microscopy images, we developed a machine learning-based user-friendly software membrane tools and incorporated it into a data management software aparecium that has been previously developed in our workgroup. For the experiments, a fluorescent ligand NAPS-Cy3B was synthesized by conjugating a dopaminergic antagonist N-(p-aminophenethyl)spiperone with a fluorophore Cy3B. The subnanomolar affinity of NAPS-Cy3B makes it a suitable ligand for the characterization of D3 receptors in live HEK293 cells. Using a microplate compatible automated widefield fluorescence microscope, together with the membrane tools software, enables the detection and quantification of ligand binding with a high-throughput. The live cell assay is suitable for the characterization of fluorescent ligand binding and also in the competition experiments for the screening of novel unlabeled dopaminergic ligands. We propose that this simple yet more native-like approach is feasible in GPCR research, as it enables the detection of ligand binding in an environment containing more components involved in the signal transduction cascade.

Neural correlates of the popular music phenomenon: evidence from functional MRI and PET imaging.

PURPOSE: Music can induce different emotions. However, its neural mechanism remains unknown. The aim of this study was to use functional magnetic resonance imaging (fMRI) and position emission tomography (PET) imaging for mapping of neural changes under the most popular music in healthy volunteers. METHODS: Blood-oxygen-level-dependent (BOLD) fMRI and monoamine receptor PET imaging with 11C-N-methylspiperone (11C-NMSP) were conducted under the popular music Gangnam Style and light music A Comme Amour in healthy subjects. PET and fMRI images were analyzed by using the Statistical Parametric Mapping software (SPM). RESULTS: Significantly increased fMRI BOLD signals were found in the bilateral superior temporal cortices, left cerebellum, left putamen and right thalamus cortex. Monoamine receptor availability was increased significantly in the left superior temporal gyrus and left putamen, but decreased in the bilateral superior occipital cortices under the Gangnam Style compared with the light music condition. Significant positive correlation was found between 11C-NMSP binding and fMRI BOLD signals in the left temporal cortex. Furthermore, increased 11C-NMSP binding in the left putamen was positively correlated with the mood arousal level score under the Gangnam Style condition. CONCLUSION: Popular music Gangnam Style can arouse pleasure experience and strong emotional response. The left putamen is positively correlated with the mood arousal level score under the Gangnam Style condition. Our results revealed characteristic patterns of brain activity associated with Gangnam Style, and may also provide more general insights into the music-induced emotional processing.

Inhibitory effects of rHP-NAP IgY against Helicobacter pylori attachment to AGS cell line.

Helicobacter pylori is a major human pathogen related to gastric adenocarcinoma and gastroduodenal diseases. Treatment of H. pylori infections is complicated by the rise of antibiotic resistance, necessitating investigation of alternative therapies. One such alternative is passive immunization by oral administration of antibacterial immunoglobulin. In the present study, chicken immunoglobulin (IgY) was used for passive immunotherapy against a major virulence factor of H. pylori, namely recombinant HP-Nap protein. Recombinant HP-Nap was prepared and used to immunize hens. IgY was purified from the eggs by polyethylene glycol precipitation method with a total IgY-HP-NAP yield of 30 mg per egg. The inhibitory effect of specific IgY on H. pylori attachment was investigated in AGS cell line infected by the bacteria. The results demonstrate the potent effect of IgY- HP-NAP in inhibition of H. pylori attachment to the AGS cells.

Structure-based drug design for dopamine D3 receptor.

D2-like receptors are members of dopamine receptors, including dopamine D2 receptor (D2R), dopamine D3 receptor (D3R), and dopamine D4 receptor (D4R), which modulate behavior, cognition, and emotion. D2-like receptors are critical targets for drug development. Particularly, D3R has been identified as a therapeutic target for antipsychotic and anti-parkinsonian drugs. Recently, the crystal structure of D3R was reported. Here we summarize the available active compounds for D3R and the structure-activity relationships (SAR) studies of them. This provides lead templates for further chemical modification. We describe the structure features of the recent crystal structure of D3R and its difference from other G protein-coupled receptors (GPCRs). We provide the recognition mechanism of the inhibitors of D3R (molecular docking results and molecular dynamics results), which illustrates the interaction between the inhibitors and critical residues of D3R. Finally, we summarize the outlook of drug development for D3R. Our study provides useful information for developing high selective, high potent antagonists and agonists of D3R.

Frightening music triggers rapid changes in brain monoamine receptors: a pilot PET study.

UNLABELLED: Frightening music can rapidly arouse emotions in listeners that mimic those from actual life-threatening experiences. However, studies of the underlying mechanism for perceiving danger created by music are limited. METHODS: We investigated monoamine receptor changes induced by frightening music using (11)C-N-methyl-spiperone ((11)C-NMSP) PET. Ten healthy male volunteers were included, and their psychophysiologic changes were evaluated. RESULTS: Compared with the baseline condition, listening to frightening music caused a significant decrease in (11)C-NMSP in the right and left caudate nuclei, right limbic region, and right paralimbic region; a particularly significant decrease in the right anterior cingulate cortex; but an increase in the right frontal occipital and left temporal lobes of the cerebral cortex. CONCLUSION: Transient fright triggers rapid changes in monoamine receptors, which decrease in the limbic and paralimbic regions but increase in the cerebral cortex.

Identification of dopamine receptor in Tetrahymena thermophila by fluorescent ligands.

Two types dopamine receptor present in the cell membrane of vertebrates. But in this study D1 receptor was identified in the invertebrate ciliates protozoan, Tetrahymena thermophila by use of fluorescent ligands. D1 specific agonist SKF-38393 binds specifically to Tetrahymena. The specific binding of SKF-38393 was encountered by equimolar addition of D1 antagonist thus showed no binding of ligands. In addition, it was also proved that the D1 specific agonist did not cross bind with the D2 type receptor due to the equimolar addition of D2 selective antagonist spiperone. Interestingly this study also showed that the dopamine receptor present in the endoplasmic reticulum and endosomes of Tetrahymena as well as cell membrane which was revealed by laser scanning microscope. Therefore, this evidence supports the existence of a D1 receptor in the ciliate protozoan.

Dopamine beta-hydroxylase-deficient mice have normal densities of D(2) dopamine receptors in the high-affinity state based on in vivo PET imaging and in vitro radioligand binding.

In vitro, D(2) dopamine receptors (DAR) can exist in low- and high-affinity states for agonists and increases of D(2) receptors in high-affinity state have been proposed to underlie DA receptor supersensitivity in vivo. Deletion of the gene for dopamine beta-hydroxylase (DBH) causes mice to become hypersensitive to the effects of psychostimulants, and in vitro radioligand binding results suggest an increased percentage of D(2) receptors in a high-affinity state. To determine whether DBH knockout mice display an increase of high-affinity state D(2) receptors in vivo, we scanned DBH knockout and control mice with the agonist PET radioligand [(11)C]MNPA, which is thought to bind preferentially to the high-affinity state of the D(2) receptor. In addition, we performed in vitro binding experiments on striatal homogenates with [(3)H]methylspiperone to measure B(max) values and the percentages of high- and low-affinity states of the D(2) receptor. We found that the in vivo striatal binding of [(11)C]MNPA was similar in DBH knockout mice and heterozygous controls and the in vitro B(max) values and percentages of D(2) receptors in the high-affinity state, were not significantly different between these two groups. In summary, our results suggest that DBH knockout mice have normal levels of D(2) receptors in the high-affinity state and that additional mechanisms contribute to their behavioral sensitivity to psychostimulants.

Competition between 11C-raclopride and endogenous dopamine in Parkinson's disease.

OBJECTIVE: The aim of this study was to understand whether the increase in 11C-raclopride binding in the striatum of patients with Parkinson's disease (PD) is associated with the depletion of endogenous dopamine. METHODS: Positron emission tomography (PET) scans of the two dopamine D2 receptor ligands, 11C-raclopride and 11C-N-methylspiperone (11C-NMSP), and the dopamine transporter ligand, 11C-2beta-carbomethoxy-3beta-(4-fluorophenyl)-tropane, were performed on five patients with PD and seven controls. The binding of each tracer was calculated by using a (region-cerebellum)/cerebellum ratio in the caudate, anterior putamen, and posterior putamen. RESULTS: In patients with PD, the 11C-raclopride to 11C-NMSP ratios in the posterior putamen, which was the subregion of the striatum with the lowest binding of 11C-2beta-carbomethoxy-3beta-(4-fluorophenyl)-tropane, were the largest among all three subregions of the striatum. In controls, the 11C-raclopride to 11C-NMSP ratios in all three subregions of the striatum were within a constant range. CONCLUSION: In patients with PD, the kinetic difference between 11C-raclopride and 11C-NMSP was found prominently in the posterior putamen, in which presynaptic degeneration occurred most profoundly. Therefore, we concluded that the increase in 11C-raclopride binding in the striatum of patients with PD was strongly associated with the depletion of endogenous dopamine. 11C-NMSP can be chosen in the place of 11C-raclopride in cases in which it may be essential to eliminate the influence of endogenous dopamine.

Selective alterations of brain dopamine D(2) receptor binding in cirrhotic patients: results of a (11)C-N-methylspiperone PET study.

Alterations of the brain dopamine system have been implicated in the neurological complications of chronic liver failure. The present study was aimed at the measurement of dopamine D(2) binding sites in cirrhotic patients by positron emission tomography (PET) using (11)C-N-methylspiperone as ligand. The regions of interest (ROI) were designated on a three-dimensional stereotaxic ROI template (3DSRT). The pixel values of twelve ROIs corrected by the pixel value of the cerebellum after 80 min static scanning were used to quantitate changes in binding. D(2) binding sites were significantly decreased in the hippocampus and thalamus of cirrhotic patients and were positively correlated with serum bilirubin levels and Child-Pugh scores and were negatively correlated with prothrombin times (thalamus). Loss of D(2) sites was greater in thalamus and hippocampus of alcoholic cirrhotics compared to non-alcoholics. Statistically significant correlations were also observed between D(2) binding sites in hippocampus, thalamus and lenticular nuclei and history of overt encephalopathy. These findings suggest that D(2) receptor binding in some regions of brain in cirrhotic patients is influenced by factors such as the severity of liver damage and history of alcohol dependency or overt encephalopathy. Alterations of D(2) receptor sites indicative of dopaminergic synaptic dysfunction could play an important role in the pathogenesis of the cognitive and motor disturbances associated with chronic liver failure.

11C-NMSP/ 18F-FDG microPET to monitor neural stem cell transplantation in a rat model of traumatic brain injury.

PURPOSE: To investigate whether (11)C-N-methylspiperone ((11)C-NMSP) microPET could be used for imaging neural stem cells (NSCs) transplantation in a rat model of traumatic brain injury. METHODS: NSCs were induced to express dopamine receptor type 2 (DRD(2)), then confirmed by RT-PCR, Western blotting and immunocytochemistry. Eighteen rats were subjected to focal traumatic brain injury in the right parietal lobe and then assigned randomly to the transplantation group and the control group. NSCs labeled with 5-bromo-2-deoxyuridine (BrdU) were transplanted into the cerebral lesion of the transplantation group. MicroPET scan using (11)C-NMSP and (18)F-FDG were performed to detect the DRD(2) expression of transplanted NSCs and the regional glucose metabolism in the cerebral lesion, respectively. Behavioral neurological function of rats were also tested. RESULTS: Histological analysis identified viable NSCs. Western blotting and immunofluorescence showed high level of NSCs-induced DRD(2) expression. Immunostaining demonstrated high levels of survived BrdU+ and DRD(2)+ donor cells in the cerebral lesion 2 weeks after transplantation. The lesion-to-normal contralateral ratio (L/N ratio) of (11)C-NMSP in the cerebral lesion decreased significantly from 97% to 68% after injury and increased dramatically to 137% 1 day after the transplantation and then decreased gradually. Glucose metabolism showed a decrease of 35% in the cerebral lesion 1 day after injury and recovered to 87% 2 weeks after transplantation. The behavioral neurological function of the transplantation group was significantly improved compared with the control group. CONCLUSIONS: This study verified that (11)C-NMSP microPET can be used to assess the NSCs-induced DRD(2) expression in rat model.

PET analysis of the 5-HT2A receptor inverse agonist ACP-103 in human brain.

The mechanisms underlying the clinical properties of atypical antipsychotics have been postulated to be mediated, in part, by interactions with the 5-HT2A receptor. Recently, it has been recognized that clinically effective antipsychotic drugs are 5-HT2A receptor inverse agonists rather than neutral antagonists. In the present study, which is part of the clinical development of the novel, selective 5-HT2A receptor inverse agonist ACP-103, we applied positron emission tomography (PET) with the radioligand [11C]N-methylspiperone ([11C]NMSP) to study the relationship between oral dose, plasma level, and uptake of ACP-103 in living human brain. The safety of drug administration was also assessed. Four healthy volunteers were examined by PET at baseline, and after the oral administration of various single doses of ACP-103. Two subjects each received 1, 5, and 20 mg doses, and two subjects each received 2, 10, and 100 mg doses, respectively. ACP-103 was well tolerated. Detectable receptor binding was observed at very low ACP-103 serum levels. Cortical [11C]NMSP binding was found to be dose-dependent and fitted well to the law of mass action. A reduction in binding was detectable after an oral dose of ACP-103 as low as 1 mg, and reached near maximal displacement following the 10-20 mg dose. In conclusion, administration of ACP-103 to healthy volunteers was found to be safe and well tolerated, and single oral doses as low as 10 mg were found to fully saturate 5-HT2A receptors in human brain as determined by PET.

A positron emission tomography study on the role of nigral lesions in parkinsonism in patients with amyotrophic lateral sclerosis.

BACKGROUND: Patients with amyotrophic lateral sclerosis (ALS) sometimes exhibit parkinsonism, but the lesion responsible for parkinsonism has not been extensively studied. OBJECTIVE: To test whether nigrostriatal system dysfunction is responsible for parkinsonism in ALS. DESIGN: From the 182 ALS patients who were admitted to our neurology ward during the past 10 years, we extracted all the patients who satisfied the criteria of both parkinsonism and ALS. SETTING: The University of Tokyo Hospital. METHODS: We conducted [(18)F]L-dopa and [(11)C]N-methylspiperone positron emission tomography and technetium Tc 99m hexamethylpropyleneamine oxime single-photon emission computed tomography studies on 5 patients with ALS manifesting overt parkinsonism. RESULTS: Two male and 3 female patients (average age, 63.2 +/- 5.8 years) had ALS for an average of 28.6 +/- 21.5 months and had parkinsonism for an average of 15.2 +/- 11.4 months. Features of their parkinsonism were characterized by outstanding bradykinesia without resting tremor or dementia. The results of positron emission tomography studies indicated normal nigrostriatal function, but those of single-photon emission computed tomography demonstrated decreased blood flow in the frontotemporal cortices. CONCLUSION: It is likely that parkinsonism in ALS is due to cortical lesions rather than nigrostriatal dysfunction and that both symptoms are the clinical manifestation of frontotemporal dementia with motor neuron diseases, including classic ALS.