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OBJECTIVES: Neuropsychiatric symptom could be useful for detecting patients with prodromal dementia. Similarities and differences in the NPSs between preclinical/prodromal Alzheimer's disease (AD) and prodromal Parkinson's disease dementia (PDD)/Dementia with Lewy bodies (DLB) may exist. This study aimed to compare the NPSs between preclinical/prodromal AD and prodromal PDD/DLB. METHODS: One hundred and three participants without dementia aged ≥50 years were included in this study. The mild behavioral impairment (MBI) total score and the MBI scores for each domain were calculated using the neuropsychiatric inventory questionnaire score. Participants were divided into five groups based on the clinical diagnosis by neurologists or psychiatrists in each institution based on the results of the amyloid positron emission tomography and dopamine transporter single photon emission computed tomography (DAT-SPECT): Group 1: amyloid-positive and abnormal DAT-SPECT, Group 2: amyloid-negative and abnormal DAT-SPECT, Group 3: amyloid-positive and normal DAT-SPECT, Group 4: mild cognitive impairment unlikely due to AD with normal DAT-SPECT, and Group 5: cognitively normal with amyloid-negative and normal DAT-SPECT. RESULTS: The MBI abnormal perception or thought content scores were significantly higher in Group 1 than Group 5 (Bonferroni-corrected p = 0.012). The MBI total score (Bonferroni-corrected p = 0.011) and MBI impulse dyscontrol score (Bonferroni-corrected p = 0.033) in Group 4 were significantly higher than those in Group 5. CONCLUSION: The presence of both amyloid and putative Lewy body pathologies may be associated with psychotic symptoms.
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Doença de Alzheimer , Disfunção Cognitiva , Demência , Doença de Parkinson , Humanos , Corpos de Lewy , Doença de Alzheimer/diagnóstico por imagemRESUMO
Tau deposits is a core feature of neurodegenerative disorder following traumatic brain injury (TBI). Despite ample evidence from post-mortem studies demonstrating exposure to both mild-repetitive and severe TBIs are linked to tau depositions, associations of topology of tau lesions with late-onset psychiatric symptoms due to TBI have not been explored. To address this issue, we assessed tau deposits in long-term survivors of TBI by PET with 11C-PBB3, and evaluated those associations with late-life neuropsychiatric outcomes. PET data were acquired from 27 subjects in the chronic stage following mild-repetitive or severe TBI and 15 healthy control subjects. Among the TBI patients, 14 were diagnosed as having late-onset symptoms based on the criteria of traumatic encephalopathy syndrome. For quantification of tau burden in TBI brains, we calculated 11C-PBB3 binding capacity (cm3), which is a summed voxel value of binding potentials (BP*ND) multiplied by voxel volume. Main outcomes of the present study were differences in 11C-PBB3 binding capacity between groups, and the association of regional 11C-PBB3 binding capacity with neuropsychiatric symptoms. To confirm 11C-PBB3 binding to tau deposits in TBI brains, we conducted in vitro PBB3 fluorescence and phospho-tau antibody immunofluorescence labelling of brain sections of chronic traumatic encephalopathy obtained from the Brain Bank. Our results showed that patients with TBI had higher 11C-PBB3 binding capacities in the neocortical grey and white matter segments than healthy control subjects. Furthermore, TBI patients with traumatic encephalopathy syndrome showed higher 11C-PBB3 binding capacity in the white matter segment than those without traumatic encephalopathy syndrome, and regional assessments revealed that subgroup difference was also significant in the frontal white matter. 11C-PBB3 binding capacity in the white matter segment correlated with the severity of psychosis. In vitro assays demonstrated PBB3-positive tau inclusions at the depth of neocortical sulci, confirming 11C-PBB3 binding to tau lesions. In conclusion, increased 11C-PBB3 binding capacity is associated with late-onset neuropsychiatric symptoms following TBI, and a close correlation was found between psychosis and 11C-PBB3 binding capacity in the white matter.
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Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/patologia , Tauopatias/diagnóstico por imagem , Adulto , Doença de Alzheimer/patologia , Encéfalo/patologia , Encefalopatia Traumática Crônica/patologia , Feminino , Humanos , Masculino , Transtornos Mentais/etiologia , Transtornos Mentais/metabolismo , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Transtornos Psicóticos/etiologia , Transtornos Psicóticos/patologia , Tauopatias/metabolismo , Substância Branca/patologia , Proteínas tau/metabolismoRESUMO
BACKGROUND: The process of birth causes stress for neonates, but additional stressors for sick neonates are a matter of concern. As analysis of heart-rate variability (HRV), which reflects autonomic activity, has demonstrated that low-frequency (LF) activity reflects overall autonomic activity, high-frequency (HF) activity reflects parasympathetic activity, and the LF/HF ratio reflects sympathetic activity, HRV has been clinically applied as a non-invasive index of physical stress. In this study, we evaluated whether HRV is useful as a stress index for neonates by analyzing it in comparison with their salivary cortisol level. METHODS: We measured the salivary cortisol level and HRV in 12 healthy neonates and 37 neonates born during between 2014 and 2016 and admitted to the neonatal intensive care unit. These examinations were performed at birth and after approximately 1 week. The changes in parameters with time were examined. RESULTS: The LF and HF values in both groups exhibited significant negative correlations with the salivary cortisol level. In those admitted to the neonatal intensive care unit, the LF and HF values were correlated with gestational age and height. In the healthy neonates, a reduced salivary cortisol level and increase in the LF and HF values were observed approximately 1 week after birth compared with the values at birth, whereas the LF/HF ratio was not correlated with the salivary cortisol level and did not change over time. CONCLUSIONS: The LF and HF values were significantly correlated with the cortisol level, suggesting their usefulness as physiological indices of stress in clinical neonatal care.
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Frequência Cardíaca , Hidrocortisona/análise , Saliva/química , Estresse Fisiológico , Eletrocardiografia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , MasculinoRESUMO
BACKGROUND: [11 C]pyridinyl-butadienyl-benzothiazole 3 is a PET imaging agent designed for capturing pathological tau aggregates in diverse neurodegenerative disorders, and would be of clinical utility for neuropathological investigations of PSP. OBJECTIVES: To explore the usefulness of [11 C]pyridinyl-butadienyl-benzothiazole 3/PET in assessing characteristic distributions of tau pathologies and their association with clinical symptoms in the brains of living PSP patients. METHODS: We assessed 13 PSP patients and 13 age-matched healthy control subjects. Individuals negative for amyloid ß PET with [11 C]Pittsburgh compound B underwent clinical scoring, MR scans, and [11 C]pyridinyl-butadienyl-benzothiazole 3/PET. RESULTS: There were significant differences in binding potential for [11 C]pyridinyl-butadienyl-benzothiazole 3 between PSP patients and healthy control subjects (P = 0.02). PSP patients exhibited greater radioligand retention than healthy control subjects in multiple brain regions, including frontoparietal white matter, parietal gray matter, globus pallidus, STN, red nucleus, and cerebellar dentate nucleus. [11 C]pyridinyl-butadienyl-benzothiazole 3 deposition in frontoparietal white matter, but not gray matter, was correlated with general severity of parkinsonian and PSP symptoms, whereas both gray matter and white matter [11 C]pyridinyl-butadienyl-benzothiazole 3 accumulations in the frontoparietal cortices were associated with nonverbal cognitive impairments. Autoradiographic and fluorescence labeling with pyridinyl-butadienyl-benzothiazole 3 was observed in gray matter and white matter of PSP motor cortex tissues. CONCLUSIONS: Our findings support the in vivo detectability of tau fibrils characteristic of PSP by [11 C]pyridinyl-butadienyl-benzothiazole 3/PET, and imply distinct and synergistic contributions of gray matter and white matte tau pathologies to clinical symptoms. [11 C]pyridinyl-butadienyl-benzothiazole 3/PET potentially provides a neuroimaging-based index for the evolution of PSP tau pathologies promoting the deterioration of motor and cognitive functions. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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Encéfalo/diagnóstico por imagem , Paralisia Supranuclear Progressiva/diagnóstico por imagem , Proteínas tau/metabolismo , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina , Autorradiografia , Benzotiazóis , Encéfalo/metabolismo , Radioisótopos de Carbono , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , TiazóisRESUMO
OBJECTIVE: Apathy is a common neuropsychological symptom in Alzheimer's disease (AD), and previous studies demonstrated that neuronal loss and network disruption in some brain regions play pivotal roles in the pathogenesis of apathy. However, contributions of tau and amyloid-ß (Aß) depositions, pathological hallmarks of AD, to the manifestation of apathy remain elusive. METHODS: Seventeen patients with AD underwent positron emission tomography (PET) with 11C-pyridinyl-butadienyl-benzothiazole 3 (11C-PBB3) and 11C-Pittsburgh compound-B (11C-PiB) to estimate tau and Aß accumulations using standardised uptake value ratio (SUVR) images. 11C-PBB3 and 11C-PiB SUVR were compared between AD patients with high and low Apathy Scale (AS) scores. Additionally, volumetric and diffusion tensor MRI was performed in those areas where any significant difference was observed in PET analyses. Correlation and path analyses among AS and estimated imaging parameters were also conducted. RESULTS: AD patients with high AS scores showed higher 11C-PBB3 SUVR in the orbitofrontal cortex (OFC) than those with low AS scores, while 11C-PiB SUVR in any brain regions did not differ between them. Elevated 11C-PBB3 SUVR in OFC, decreased OFC thickness and decreased fractional anisotropy (FA) in the uncinate fasciculus (UNC), which is structurally connected to OFC, correlated significantly with increased scores of the AS. Path analysis indicated that increased 11C-PBB3 SUVR in OFC affects apathy directly and through reduction of OFC thickness and subsequent decrease of FA in UNC. CONCLUSIONS: The present findings suggested that tau pathology in OFC may provoke focal neurotoxicity in OFC and the following disruption of the OFC-UNC network, leading to the emergence and progression of apathy in AD.
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Doença de Alzheimer/metabolismo , Apatia/fisiologia , Rede Nervosa/metabolismo , Córtex Pré-Frontal/diagnóstico por imagem , Proteínas tau/metabolismo , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/metabolismo , Imagem de Tensor de Difusão , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Tomografia por Emissão de PósitronsRESUMO
PURPOSE: The histamine H3 receptors are presynaptic neuroreceptors that inhibit the release of histamine and other neurotransmitters. The receptors are considered a drug target for sleep disorders and neuropsychiatric disorders with cognitive decline. We developed a novel PET ligand for the H3 receptors, [(11)C]TASP0410457 ([(11)C]TASP457), with high affinity, selectivity and favorable kinetic properties in the monkey, and evaluated its kinetics and radiation safety profile for quantifying the H3 receptors in human brain. METHODS: Ten healthy men were scanned for 120 min with a PET scanner for brain quantification and three healthy men were scanned for radiation dosimetry after injection of 386 ± 6.2 MBq and 190 ± 7.5 MBq of [(11)C]TASP457, respectively. For brain quantification, arterial blood sampling and metabolite analysis were performed using high-performance liquid chromatography. Distribution volumes (V T) in brain regions were determined by compartment and graphical analyses using the Logan plot and Ichise multilinear analysis (MA1). For dosimetry, radiation absorbed doses were estimated using the Medical Internal Radiation Dose scheme. RESULTS: [(11)C]TASP457 PET showed high uptake (standardized uptake values in the range of about 3 - 6) in the brain and fast washout in cortical regions and slow washout in the pallidum. The two-tissue compartment model and graphical analyses estimated V T with excellent identification using 60-min scan data (about 16 mL/cm(3) in the pallidum, 9 - 14 in the basal ganglia, 6 - 9 in cortical regions, and 5 in the pons), which represents the known distribution of histamine H3 receptors. For parametric imaging, MA1 is recommended because of minimal underestimation with small intersubject variability. The organs with the highest radiation doses were the pancreas, kidneys, and liver. The effective dose delivered by [(11)C]TASP457 was 6.9 µSv/MBq. CONCLUSION: [(11)C]TASP457 is a useful novel PET ligand for the investigation of the density of histamine H3 receptors in human brain.
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Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Radioisótopos de Carbono/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Receptores Histamínicos H3/metabolismo , Adulto , Transporte Biológico , Radioisótopos de Carbono/sangue , Radioisótopos de Carbono/farmacocinética , Voluntários Saudáveis , Humanos , Cinética , Ligantes , Masculino , RadiometriaRESUMO
OBJECTIVE: To characterize the distribution of tau pathology in patients with amyotrophic lateral sclerosis/parkinsonism dementia complex on the Kii Peninsula (Kii ALS/PDC) by tau PET using [11C]PBB3 as ligand. METHODS: This is a cross-sectional study of 5 patients with ALS/PDC and one asymptomatic participant with a dense family history of ALS/PDC from the Kii Peninsula who took part in this study. All were men, and their age was 76 ± 8 (mean ± SD) years. Thirteen healthy men (69 ± 6 years) participated as healthy controls (HCs). Dynamic PET scans were performed following injection of [11C]PBB3, and parametric PET images were generated by voxel-by-voxel calculation of binding potential (BP* ND) using a multilinear reference tissue model. [11C] Pittsburgh compound B (PiB) PET, MRI, and cognitive tests were also performed. RESULTS: A voxel-based comparison of [11C]PBB3 BP* ND illustrated PET-detectable tau deposition in the cerebral cortex and white matter, and pontine basis including the corticospinal tract in Kii ALS/PDC patients compared with HCs (uncorrected p < 0.05). Group-wise volume of interest analysis of [11C]PBB3 BP* ND images showed increased BP* ND in the hippocampus and in frontal and parietal white matters of Kii ALS/PDC patients relative to HCs (p < 0.05, Holm-Sidak multiple comparisons test). BP* ND in frontal, temporal, and parietal gray matters correlated with Mini-Mental State Examination scores in Kii ALS/PDC patients (p < 0.05). All Kii ALS/PDC patients were negative for [11C]PiB (ß-amyloid) except one with marginal positivity. CONCLUSION: [11C]PBB3 PET visualized the characteristic topography of tau pathology in Kii ALS/PDC, corresponding to clinical phenotypes of this disease.
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Esclerose Lateral Amiotrófica/diagnóstico por imagem , Esclerose Lateral Amiotrófica/metabolismo , Encéfalo/diagnóstico por imagem , Transtornos Parkinsonianos/diagnóstico por imagem , Transtornos Parkinsonianos/metabolismo , Proteínas tau/metabolismo , Idoso , Idoso de 80 Anos ou mais , Benzotiazóis/farmacocinética , Encéfalo/efeitos dos fármacos , Estudos Transversais , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Japão/epidemiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Trítio/farmacocinéticaRESUMO
We report a patient of baroreflex failure two years after bilateral cervical internal carotid artery (ICA) revascularization. A 76-year-old hypertensive man was admitted to our hospital after suffering multiple syncopal events for the past 2 years prior to admission. He received bilateral surgical and endovascular revascularization for stenotic lesions of the ICA orifices 4 years ago. Intervention consisted of carotid endarterectomy and carotid stenting for the right and left ICAs, respectively. Head T2-weighted magnetic resonance images demonstrated multiple high intensity signals in the basal ganglia bilaterally. To investigate his autonomic function, head-up tilt test, 24-hour ambulatory blood pressure measurements, and Valsalva's maneuver were performed. The patient demonstrated marked orthostatic hypotension without increment of heart rate, increased variability of blood pressure and abnormal hypertensive surges in a single 24 hour period, and abnormal response of heart rate during Valsalva's maneuver. These findings were indicative of impaired baroreflex-mediated vasomotor and heart rate control. Other examinations involving hematological analysis, cardiac function assessment, and scintigraphy for pheochromocytoma were within normal limits except for a marked increase in plasma norepinephrine during hypertensive surge. We therefore considered that he had baroreflex failure resulting from previous bilateral ICA orifice revascularization. The patient was given diazepam during hospitalization. After then, his blood pressure stabilized somewhat and syncopal attacks were controlled. Our case suggests that patients, who undergo bilateral ICA orifice revascularization and present with syncopal attacks, should be considered baroreflex failure even if the patient is post-operative several years. Long-term follow up should therefore be necessitated in patients who undergo bilateral carotid revascularization.
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Barorreflexo/fisiologia , Artéria Carótida Interna/cirurgia , Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas , Hipertensão/etiologia , Complicações Pós-Operatórias , Antagonistas Adrenérgicos alfa/administração & dosagem , Idoso , Diagnóstico Diferencial , Diazepam/administração & dosagem , Doxazossina/administração & dosagem , Quimioterapia Combinada , Seguimentos , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipotensão Ortostática/etiologia , Masculino , Stents , Síncope/etiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
INTRODUCTION: Amyloid-ß (Aß) and tau accumulations may occur independently and concurrently as exemplified by primary age-related tauopathy and Alzheimer's disease (AD), respectively. Interactions between Aß and tau accumulations and their influence on clinical features, however, are still unclear. METHODS: Associations among clinical symptoms, gray-matter volume, regional tau, and Aß deposition assessed by positron emission tomography with [11C]pyridinyl-butadienyl-benzothiazole 3 (PBB3) and [11C]Pittsburgh compound-B (PiB), were evaluated in 17 AD, 9 mild cognitive impairment due to AD, and 28 PiB(-)-cognitive healthy controls (HCs). RESULTS: High tau burden was associated with aging and low-level education in PiB(-)-HC and AD-spectrum groups, and with high Aß burden and low-level education in all subjects. It was not Aß but tau accumulation that showed significant associations with cognitive performance even in PiB(-)-HC. DISCUSSION: The present study indicated aging and low-level education after Aß would be enhancers for tau pathology, associated with neurodegeneration and cognitive impairment in healthy and diseased elderly individuals.
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BACKGROUND: Sleep has been reported to be an important factor in bone metabolism, and sympathetic nervous system activity has been reported to regulate bone metabolism. In this study, we evaluated the association between sleep, sympathetic nervous system activity, and bone mass. METHODS: The study subjects were 221 individuals (108 males; 113 females; mean age: 55.1±7.0years) divided into two groups: those who slept for less than 6h a day (short sleep [SS] group), and those who slept 6h or longer (normal sleep [NS] group). The groups were compared with regard to lifestyle, cortical bone thickness, cancellous bone density, bone metabolism markers, blood leptin levels, and sympathetic nervous system activity as evaluated by heart rate variability analysis. RESULTS: Significant differences were observed between the two groups in cortical bone thickness, blood TRACP-5b, and leptin levels. The L/H ratio (an index of sympathetic nervous system activity) was higher in the SS group than in the NS group. Significant negative correlations were observed between cortical bone thickness and both the L/H ratio and leptin levels, and a significant positive correlation was observed between the L/H ratio and leptin levels. CONCLUSIONS: Short sleep was associated with a decline in cortical bone thickness due to the promotion of bone resorption and sympathetic nervous system hyperactivity in the middle-aged group. Leptin levels and cortical bone thickness were found to be closely related, suggesting that cortical bone mass may be regulated via interaction with the leptin-sympathetic nervous system.
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Densidade Óssea/fisiologia , Osso Cortical/fisiopatologia , Frequência Cardíaca/fisiologia , Leptina/sangue , Transtornos do Sono-Vigília/fisiopatologia , Fosfatase Alcalina/sangue , Biomarcadores/sangue , Densitometria , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatase Ácida Resistente a Tartarato/sangueRESUMO
BACKGROUND: α-Amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor is a primary mediator of fast glutamatergic excitatory signaling in the brain and has been implicated in diverse neuropsychiatric diseases. We recently developed a novel positron emission tomography (PET) ligand, 2-(1-(3-([11C]methylamino)phenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl) benzonitrile ([11C]HMS011). This compound is a radiolabelled derivative of perampanel, an antiepileptic drug acting on AMPA receptors, and was demonstrated to have promising in vivo properties in the rat and monkey brains. In the current study, we performed a human PET study using [11C]HMS011 to evaluate its safety and kinetics. Four healthy male subjects underwent a 120-min PET scan after injection of [11C]HMS011. Arterial blood sampling and metabolite analysis were performed to obtain parent input functions for three of the subjects using high-performance liquid chromatography. Regional distribution volumes (V Ts) were calculated based on kinetic models with and without considering radiometabolite in the brain. The binding was also quantified using a reference tissue model with white matter as reference. RESULTS: Brain uptake of [11C]HMS011 was observed quickly after the injection, followed by a rapid clearance. Three hydrophilic and one lipophilic radiometabolites appeared in the plasma, with notable individual variability. The kinetics in the brain with apparent radioactivity retention suggested that the lipophilic radiometabolite could enter the brain. A dual-input graphical model, an analytical model designed in consideration of a radiometabolite entering the brain, well described the kinetics of [11C]HMS011. A reference tissue model showed small radioligand binding potential (BP*ND) values in the cortical regions (BP*ND = 0-0.15). These data suggested specific binding component of [11C]HMS011 in the brain. CONCLUSIONS: Kinetic analyses support some specific binding of [11C]HMS011 in the human cortex. However, this ligand may not be suitable for practical AMPA receptor PET imaging due to the small dynamic range and metabolite in the brain.
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We report a 60-year-old man with grade III astrocytoma, who presented with status epilepticus. The initial MRI did not demonstrate typical findings of an astrocytoma but rather showed reversible posterior leukoencephalopathy syndrome (RPLS). N-Isopropil-p-[I] iodoamphetamine single photon emission computed tomography (SPECT) demonstrated hyperperfusion in this area. A brain tumor should be considered and the patient carefully followed by MRI, even if the MRI white matter lesion pattern suggests RPLS. This is especially relevant in the presence of atypical findings for RPLS on SPECT.
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Astrocitoma/diagnóstico , Encefalopatias/diagnóstico , Lobo Occipital/patologia , Astrocitoma/complicações , Astrocitoma/diagnóstico por imagem , Encefalopatias/complicações , Encefalopatias/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Lobo Occipital/diagnóstico por imagem , Estado Epiléptico/etiologia , Tomografia Computadorizada de Emissão de Fóton Único/métodosRESUMO
Objective Regional cerebral blood flow (rCBF) imaging with single-photon emission computed tomography (SPECT) is useful in the early diagnosis of dementia. We aimed to investigate the association between the rCBF and various domains related to the memory function in elderly subjects with subjective cognitive impairment (SCI). Methods Thirty-two subjects with SCI were included in the present study. Patients with dementia and mild cognitive impairment (MCI) were excluded based on the presence of logical memory impairment. N-isopropyl-p-[123I]-iodoamphetamine SPECT was performed and Wechsler Memory Scale-Revised (WMS-R) was administered to all subjects (mean age, 68.4 years; average Mini-Mental State Examination score, 27.6). The SPECT results were analyzed using the easy Z-score imaging system and the voxel-based stereotactic extraction estimation method. Correlation analyses were performed to investigate the correlation between the mean positive Z-scores in the decrease of the rCBF and the WMS-R indices. Results The SPECT study indicated marked hypoperfusion in some areas, including the bilateral temporal areas, the caudate, and the thalamus, in these subjects in comparison to the normal database. The decrease in the rCBF that was observed in several regions, including the left precuneus and left inferior frontal gyrus (LIFG), showed a significant negative correlation with several indices of the memory function, particularly visual memory. Conclusion The regional hypoperfusion observed in the study using the voxel-based stereotactic extraction estimation method suggest that the regional cerebral dysfunction is associated with the memory function of patients with SCI, even though the subjects in the present study were cognitively intact. The correlation analysis with the WMS-R suggested the contribution of the LIFG to the memory function and indicated the significance of visual memory dysfunction in the neuropsychological assessment to determine the stage of SCI.
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Córtex Cerebral/irrigação sanguínea , Circulação Cerebrovascular , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Demência/diagnóstico , Testes Neuropsicológicos , Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Córtex Cerebral/diagnóstico por imagem , Transtornos Cognitivos/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Feminino , Humanos , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Lobo Temporal/irrigação sanguínea , Lobo Temporal/diagnóstico por imagemRESUMO
We herein report the case of a 69-year-old woman with Charcot-Marie-Tooth Disease type 2J (CMT2J) who presented with Adie's pupil, deafness, and urinary disturbance in addition to motor symptoms. On autonomic investigation, the coefficient of variation of the R-R intervals was decreased, and a urodynamic analysis showed a hypotonic bladder. A heart rate variability analysis revealed a decreased high frequency component and low frequency/high frequency ratio. Orthostatic hypotension was not present, and the sympathetic skin response and cardiac scintigraphy using (123)I-metaiodobenzylguanidine were normal. A gene analysis showed a known heterozygous mutation associated with CMT2J in myelin protein zero exon 3, resulting in the substitution of threonine to methionine at position 124. Our case suggests that mainly the parasympathetic autonomic function is disturbed in CMT2J.
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Doenças do Sistema Nervoso Autônomo/complicações , Doença de Charcot-Marie-Tooth/complicações , Doença de Charcot-Marie-Tooth/genética , Perda Auditiva Neurossensorial/complicações , Perda Auditiva Neurossensorial/genética , Proteína P0 da Mielina/genética , Idoso , Éxons , Feminino , Humanos , Mutação , Polimorfismo de Nucleotídeo ÚnicoRESUMO
AIM: To understand the characteristics of peripheral immunity in patients with Parkinson's disease (PD), we investigated the natural killer (NK) cell activity and lymphocyte subpopulations including regulatory T (Treg) cells and type 17 helper T (Th17) cells. METHODS: Peripheral blood was collected from 29 PD patients (mean age 70.4 years) and 30 healthy controls (mean age 68.9 years). NK cell activity was measured by a calcein acetoxymethyl ester release assay using NK-sensitive K562 cells, peripheral NK cells and lymphocytes subsets were analyzed using flow cytometry techniques. RESULTS: Comparison of the two groups demonstrated that the percentage of NK cells increased and that of helper T cells, particularly type 1 (Th1), decreased in patients with PD. There was no evidence of Th1/Th2 or Treg/Th17 cell predominance in PD. Moreover, the increase of NK cells and the decrease of Th1 cells correlated with Unified Parkinson's Disease Rating Scale scores and the heart-to-mediastinum ratios based on myocardial (123) I-metaiodobenzylguanidine uptake, both of which represent disease severity in patients with PD. CONCLUSION: Our investigation indicates that a certain proportion of NK cells and other lymphocytes in the peripheral blood of patients with PD and their association with disease severity may reflect the effect of innate immunity in patients with PD in addition to the effect of dopaminergic-related agents.
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Imunidade Inata , Ativação Linfocitária/imunologia , Subpopulações de Linfócitos/imunologia , Doença de Parkinson/imunologia , Idoso , Feminino , Citometria de Fluxo , Humanos , Contagem de Linfócitos , Masculino , Doença de Parkinson/sangueRESUMO
Patients with Parkinson's disease (PD) often suffer from non-motor symptoms, including sleep and autonomic dysfunctions, controlled by circadian regulation. To evaluate the alteration of circadian rhythm in PD patients, we investigated both rest activities and autonomic functions. Twenty-seven patients with idiopathic PD and 30 age-matched control subjects were recruited. Group comparisons of controls (mean age: 68.93 years), early-PD patients classified as Hoehn-Yahr (HY) stage 1&2 (mean age: 70.78 years), and advanced-PD as HY 3&4 (mean age: 68.61 years) were conducted. Measurement of rest activities was performed using Actigraph for 7 continuous days, and included measuring rhythm patterns (activity patterns recorded in or out of bed) and circadian rhythm amplitudes (power of the cycle being closest to 24h). A power spectral analysis of heart rate variability (HRV) using 24-hour ambulatory ECG was also performed. The actigraphic measurements indicated that statistically PD patients have lower activity levels when out of bed and higher activity levels when in bed, and that, the circadian rest-activity rhythm in PD decreases with disease severity. The HRV analysis showed that the total frequency component and low frequency/high frequency ratio were low in PD patients, suggesting that autonomic activities and the circadian rhythm of the sympathetic nervous system are attenuated in PD. This study elucidated the disorganization in the rest activities and HRV of PD patients as well as the gradual alterations in the circadian rhythm. The circadian rhythm disturbances are important to consider the mechanism of non-motor symptoms that occur from early stage of PD.
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Sistema Nervoso Autônomo/fisiopatologia , Ritmo Circadiano/fisiologia , Doença de Parkinson/fisiopatologia , Descanso/fisiologia , Actigrafia , Idoso , Eletrocardiografia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We describe a 72-year-old man who developed subacute onset parkinsonism caused by neuro-Sweet disease (NSD). Magnetic resonance imaging of this patient's brain suggested inflammation of the bilateral basal ganglia and amygdalae. Clinical symptoms and MRI findings gradually improved without medication. However, his parkinsonism recurred one month after discharge from the hospital, at which time he was treated with corticosteroids, resulting in improvement again. His clinical course and human leukocyte antigen typing suggested that he was suffering from NSD. This case is the first report of NSD presenting with self-remitting and reversible parkinsonism.
Assuntos
Transtornos Parkinsonianos/diagnóstico , Transtornos Parkinsonianos/etiologia , Síndrome de Sweet/complicações , Síndrome de Sweet/diagnóstico , Corticosteroides/uso terapêutico , Idoso , Humanos , Masculino , Transtornos Parkinsonianos/tratamento farmacológico , Recidiva , Síndrome de Sweet/tratamento farmacológicoRESUMO
OBJECTIVE: Central autonomic impairment due to acute cerebral infarction is known to lead to excessively high blood pressure and tachycardia. The mechanism by which these symptoms occur in patients with supratentorial lesions has not been elucidated. The objective of this study was to evaluate the autonomic dysfunction that occurs in these patients. METHODS: Seventy-seven ischemic stroke patients (65·8 years) with an acute ischemic cerebral infarction underwent comprehensive clinical evaluation that included laboratory tests and a 24 hour electrocardiogram. These patients were classified into one of the following two groups: those with either a single, supratentorial symptomatic small-vessel occlusion (lacunar infarction; n=47; Group S), or a large-artery atherosclerosis (n=30; Group A); 31 unimpaired subjects served as controls (Group C). RESULTS: High frequency power spectrum (HF), which is thought to be a reflection of parasympathetic activity, was significantly reduced in all patient groups (p<0·01) at the time of admission compared to controls. Seven days later, only the HF values in Group A were still reduced. The correlations between the patients' NIHSS scores and their HF were statistically significant in each group, and multiple adjusted relative risk of HF value was 1·31 (95% CI: 1·02-2·11). The HF in Group S was found to be particularly diminished in patients who had an infarction in either the putamen or thalamus so that these ganglia may be key lesions of central autonomic network. CONCLUSION: Our data suggest that patients with a supratentorial acute stage cerebral infarction may display a reduced parasympathetic regulation and relative increase in sympathetic output.