RESUMEN
BACKGROUND: Cerebral microbleeds (CMBs) detected on susceptibility-weighted imaging (SWI) are associated with cerebral small vessel disease. Chronic kidney disease and microalbuminuria have been associated with the presence of CMBs in stroke patients. Urinary immunoglobulin G (IgG) is measured to document glomerular injury; however, the relationship between urinary IgG and CMBs is unknown. METHODS: We retrospectively enrolled consecutive patients who had been admitted with transient ischemic attack (TIA) or ischemic stroke and identified those who had undergone SWI and a spot urine test. The location of CMBs was classified on magnetic resonance imaging as strictly lobar, deep/infratentorial (D/I), or mixed areas. We analyzed the association between urinary IgG and the presence and location of CMBs. RESULTS: We included 298 patients (86 female, median age 70 years, median eGFR 65.8 mL/min/1.73 m2). Positive urinary IgG and CMB results were found in 58 (19%) and 160 patients (54%), respectively. Urinary IgG positivity was significantly associated with CMBs compared with non-CMBs (28% vs. 9%, p < 0.001), and with D/I or mixed CMBs compared with non-D/I or mixed CMBs (34% vs. 10%, p < 0.001). Multivariate analysis revealed that urinary IgG and hypertension positivity were strongly associated with D/I or mixed CMBs (OR 3.479, 95% CI: 1.776-6.818, p < 0.001; OR 3.415, 95% CI: 1.863-6.258, p < 0.001). CONCLUSIONS: Urinary IgG was associated with the prevalence of D/I or mixed location CMBs in TIA or ischemic stroke patients. Our findings provide new insights into the association between urinary IgG and the distribution of CMBs.
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Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Femenino , Anciano , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/diagnóstico por imagen , Hemorragia Cerebral/epidemiología , Estudios Retrospectivos , Inmunoglobulina G , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Accidente Cerebrovascular Isquémico/complicaciones , Factores de RiesgoRESUMEN
BACKGROUND: Monotherapy with monoamine oxidase B (MAO-B) inhibitors enhances the level of endogenous dopamine in treatment for Parkinson's disease (PD) and provides some benefits. Certain neuropsychiatric functions are also regulated by central dopaminergic activity. AIM: To investigate the relationship of the efficacy of monotherapy with MAO-B inhibitors on motor symptoms in PD with baseline cognitive function. PATIENTS AND METHODS: Outcomes were examined for 27 consecutive drug-naïve PD patients who received initial treatment with a MAO-B inhibitor (selegiline: 11, rasagiline: 16). Selegiline was titrated to an optimal dose. The dose of rasagiline was fixed at 1 mg/day. Motor symptoms were assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III before treatment and after the efficacy reached a plateau within 19 weeks after drug initiation, and the % improvement in motor symptoms was calculated. Pre-treatment cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and Frontal Assessment Battery (FAB). Correlations of % improvement in motor symptoms and baseline cognitive assessments were examined using Spearman correlation coefficients and multiple regression analysis. RESULTS: In all patients, the mean % improvement in motor symptoms was 46.5% (range 0-83.3%). Spearman correlation coefficients showed the % improvement in motor symptoms was correlated with FAB (r = 0.631, p < 0.001). In multiple regression analysis with patient background factors as independent variables, only FAB was associated with improvement in motor symptoms in the MAO-B group. CONCLUSION: Better FAB scores predict a significant improvement in motor symptoms with treatment with MAO-B inhibitors, suggesting high activity of endogenous dopamine.
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Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/tratamiento farmacológico , Selegilina/uso terapéutico , Selegilina/farmacología , Antiparkinsonianos/uso terapéutico , Dopamina , Inhibidores de la Monoaminooxidasa/uso terapéutico , Indanos/uso terapéutico , Dopaminérgicos/uso terapéutico , MonoaminooxidasaRESUMEN
BACKGROUND: Levodopa remains the most effective symptomatic treatment for Parkinson's disease (PD) more than 50 years after its clinical introduction. However, the onset of motor complications can limit pharmacological intervention with levodopa, which can be a challenge when treating PD patients. Clinical data suggest using the lowest possible levodopa dose to balance the risk/benefit. Istradefylline, an adenosine A2A receptor antagonist indicated as an adjunctive treatment to levodopa-containing preparations in PD patients experiencing wearing off, is currently available in Japan and the US. Preclinical and preliminary clinical data suggested that adjunctive istradefylline may provide sustained antiparkinsonian benefits without a levodopa dose increase; however, available data on the impact of istradefylline on levodopa dose titration are limited. The ISTRA ADJUST PD study will evaluate the effect of adjunctive istradefylline on levodopa dosage titration in PD patients. METHODS: This 37-week, multicenter, randomized, open-label, parallel-group controlled study in PD patients aged 30-84 years who are experiencing the wearing-off phenomenon despite receiving levodopa-containing medications ≥ 3 times daily (daily dose 300-400 mg) began in February 2019 and will continue until February 2022. Enrollment is planned to attain 100 evaluable patients for the efficacy analyses. Patients will receive adjunctive istradefylline (20 mg/day, increasing to 40 mg/day) or the control in a 1:1 ratio, stratified by age, levodopa equivalent dose, and presence/absence of dyskinesia. During the study, the levodopa dose will be increased according to symptom severity. The primary study endpoint is the comparison of the cumulative additional dose of levodopa-containing medications during the treatment period between the adjunctive istradefylline and control groups. Secondary endpoints include changes in efficacy rating scales and safety outcomes. DISCUSSION: This study aims to clarify whether adjunctive istradefylline can reduce the cumulative additional dose of levodopa-containing medications in PD patients experiencing the wearing-off phenomenon, and lower the risk of levodopa-associated complications. It is anticipated that data from ISTRA ADJUST PD will help inform future clinical decision-making for patients with PD in the real-world setting. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCTs031180248 ; registered 12 March 2019.
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Levodopa , Enfermedad de Parkinson , Antagonistas del Receptor de Adenosina A2/farmacología , Antagonistas del Receptor de Adenosina A2/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antiparkinsonianos/uso terapéutico , Humanos , Levodopa/efectos adversos , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Enfermedad de Parkinson/tratamiento farmacológico , Purinas/farmacología , Purinas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Advanced glycation end products (AGEs) are suggested to play a potential role in the progression of Parkinson's disease (PD). The association between urinary levels of pentosidine, one of the best-characterized AGEs, and clinical conditions such as motor severity and cognition were investigated in patients with PD. Data on the clinical characteristics and urinary levels of pentosidine for 44 drug-naïve patients aged 60 years or older with PD were collected. The association between urinary pentosidine levels and severity of motor symptoms and cognition was analyzed using the Montreal Cognitive Assessment Scale (MoCA). Urinary pentosidine values increased with age (R2 = 0.286, p < 0.001) and were negatively correlated with the MoCA score (R2 = 0.255, p = 0.001). Urinary pentosidine levels were significantly correlated with age (r = 0.535, p < 0.001), Hoehn-Yahr stage (r = 0.340, p < 0.05), and total MoCA score (r = - 0.505, p < 0.001). Multiple linear regression analysis showed that older age (ß = 0.543; 95% confidence interval [CI] 0.300, 1.307; p = 0.003) was significantly associated with severity of motor symptoms, and that older age (ß = - 0.456; 95% CI - 0.287, - 0.054; p = 0.005) and urinary pentosidine levels (ß = - 0.311; 95% CI - 0.428, - 0.004; p = 0.046) were significantly associated with a lower MoCA score. Urinary pentosidine levels were significantly associated with lower cognition in drug-naïve PD patients. These findings have important clinical implications and suggest that pentosidine may be a potential marker for cognitive impairment in early PD.
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Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/psicología , Cognición , Arginina , LisinaRESUMEN
OBJECTIVE: To determine transcranial Doppler ultrasonography (TCD) parameters related to unfavorable outcomes, and to clarify the correlations between those parameters and heart functions in acute ischemic stroke without major vessel stenoses and occlusions. MATERIALS AND METHODS: Patients were selected from a comprehensive stroke center between October 2012 and June 2019. Inclusion criteria were: 1) acute ischemic stroke without major vessel stenoses and occlusions; and 2) ability to measure blood flow in the middle cerebral artery by TCD. Unfavorable outcomes were defined as a modified Rankin Scale score of 2-6 at 3 months after onset. First, we investigated TCD parameters related to unfavorable outcomes. Second, correlations between those parameters and heart functions as assessed by transthoracic echocardiography were evaluated. RESULTS: We screened 1,527 consecutive ischemic stroke patients, including 130 patients (109 [83%] male; median age, 60 years). Middle cerebral artery pulsatility index (M1 PI) (Odds ratio (OR) 0.057, 95%confidence interval (CI) 0.007-0.494, p = 0.009) was independently associated with unfavorable outcomes. Concerning the relation between M1 PI and heart functions, peak early filling velocity/velocity of mitral annulus early diastolic motion (E/e') (OR 1.195, 95%CI 1.011-1.413, p = 0.037) was a factor independently associated with high M1 PI. CONCLUSIONS: High M1 PI predicts unfavorable outcome regardless of ischemic stroke subtype without major vessel stenoses and occlusions. High M1 PI correlates with high E/e', suggesting diastolic dysfunction.
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Accidente Cerebrovascular Isquémico , Arteria Cerebral Media , Cardiomiopatías/epidemiología , Humanos , Accidente Cerebrovascular Isquémico/fisiopatología , Accidente Cerebrovascular Isquémico/terapia , Masculino , Persona de Mediana Edad , Arteria Cerebral Media/diagnóstico por imagen , Arteria Cerebral Media/fisiopatología , Pronóstico , Ultrasonografía Doppler TranscranealRESUMEN
Parkinson's disease (PD) impairs various cognitive functions, including time perception. Dysfunctional time perception in PD is poorly understood, and no study has investigated the rehabilitation of time perception in patients with PD. We aimed to induce the recovery of time perception in PD patients and investigated the potential relationship between recovery and cognitive functions/domains other than time perception. Sixty patients with PD (27 females) and 20 healthy controls (10 females) were recruited. The participants underwent a feedback training protocol for 4 weeks to improve the accuracy of subjective spatial distance or time duration using a ruler or stopwatch, respectively. They participated in three tests at weekly intervals, each comprising 10 types of cognitive tasks and assessments. After duration feedback training for 1 month, performance on the Go/No-go task, Stroop task, and impulsivity assessment improved in patients with PD, while no effect was observed after distance feedback training. Additionally, the effect of training on duration production correlated with extended reaction time and improved accuracy in the Go/No-go and Stroop tasks. These findings suggest that time perception is functionally linked to inhibitory systems. If the feedback training protocol can modulate and maintain time perception, it may improve various cognitive/psychiatric functions in patients with PD. It may also be useful in the treatment of diseases other than PD that cause dysfunctions in temporal processing.
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Cognición/fisiología , Enfermedad de Parkinson/psicología , Enfermedad de Parkinson/terapia , Tiempo de Reacción/fisiología , Percepción Espacial/fisiología , Percepción del Tiempo/fisiología , Estimulación Acústica/métodos , Anciano , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Distribución AleatoriaRESUMEN
Striatal dopamine depletion is associated with not only motor symptom but also non-motor symptoms in patients with Parkinson's disease (PD). The purpose is to elucidate the relation between heart rate variability (HRV) and dopaminergic depletion in specific striatal subregions. The subjects were 84 patients with newly diagnosed untreated PD. All patients underwent striatal 123I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) dopamine transporter single-photon emission computed tomography (DAT-SPECT). DaTQUANT software (GE Healthcare) was used as a semi-quantitative tool to analyze DAT-SPECT data. Association of HRV with dopaminergic depletion in specific striatal subregions was examined. HRV was related to dopamine depletion in the caudate and anterior putamen, especially the left side, after controlling for age, hemoglobin A1c level, disease duration, motor severity and global cognition on multiple regression analysis (left caudate p = 0.012). HRV was closely related to striatal dopamine depletion, especially in the left associative striatum, in patients with PD.
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Dopamina , Enfermedad de Parkinson , Cuerpo Estriado/diagnóstico por imagen , Cuerpo Estriado/metabolismo , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Frecuencia Cardíaca , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único/métodos , TropanosRESUMEN
OBJECTIVES: Minor hallucinations (MHs), including sense of presence, passage hallucinations, and visual illusions, have been reported in Parkinson's disease (PD). Here, we investigated the prevalence and associated risk factors for MHs according to appearance time. METHODS: Data on the clinical characteristics and the appearance time of MHs for 100 PD patients were collected using a questionnaire and analyzed. MHs were classified into two groups according to the time when MHs appeared: MHs appearing while awake during the daytime (dMHs) and MHs appearing at arousal from sleep during the night or early morning (aMHs). RESULTS: Thirty-eight patients (38%) experienced MHs. dMHs and aMHs were present in 21 (21%) and 28 patients (28%), respectively. Compared to patients without MHs, patients with dMHs had more severe motor symptoms, longer disease duration, higher levodopa equivalent daily dose (LEDD), and higher rates of cognitive impairment and visual hallucinations during the daytime, whereas patients with aMHs had a higher rate of rapid eye movement sleep behavior disorder (RBD), longer disease duration, higher LEDD, and higher dopamine agonist dosage. Logistic regression analysis showed that cognitive impairment was significantly associated with dMHs (odds ratio (OR) 7.292, p = .001), and that RBD (OR 8.306, p < .001) and LEDD (OR 1.002, p = .049) were significantly associated with aMHs. CONCLUSIONS: Patients with MHs have different clinical characteristics according to the time when MHs appear. These findings have important clinical and prognostic implications and suggest appropriate therapeutic options for psychotic symptoms.
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Alucinaciones/etiología , Enfermedad de Parkinson/complicaciones , Anciano , Femenino , Alucinaciones/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de RiesgoRESUMEN
PURPOSE: Delayed orthostatic hypotension (DOH), a fall in blood pressure after a 3-min cutoff, is clinically meaningful. The aim of this study was to elucidate the clinical and neuroendocrinological characteristics of DOH in patients with Parkinson's disease (PD). METHODS: A total of 132 patients with newly diagnosed PD were enrolled. Baseline clinical characteristics, including olfactory function, and changes in norepinephrine (NE) and vasopressin (ADH) concentrations during the head-up tilt test (HUT), were examined. RESULTS: Fifty-five patients (42%) had classical orthostatic hypotension (COH), and 19 patients (14%) had DOH. Patients with COH and DOH tended to have more severe hyposmia than patients without OH. A multivariate linear regression model showed that hyposmia was associated with DOH and COH. The increase of heart rate against the fall in blood pressure was significantly lower in patients with COH and DOH than those without OH. The NE levels at supine rest and after upright tilting were lower in the COH group than in the PD without OH and DOH groups. The levels of ADH were higher in the DOH group than in the COH group at supine rest and higher than in the PD without OH group after upright tilting. There was no significant difference in the cardiac 123I-MIBG scintigraphy between the COH and DOH groups. CONCLUSION: Compared with patients without OH, patients with DOH had severe hyposmia. Relatively preserved peripheral sympathetic nervous system function in patients with DOH suggests that DOH might be an early and milder form of OH in PD.
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Hipotensión Ortostática , Enfermedad de Parkinson , Presión Sanguínea , Frecuencia Cardíaca , Humanos , Hipotensión Ortostática/etiología , Enfermedad de Parkinson/complicaciones , Pruebas de Mesa InclinadaRESUMEN
BACKGROUND AND AIM: Some patients with Parkinson's disease (PD) present with pareidolia, an illusion of a meaningless stimulus as a familiar object known to the observer. Since the striatum is associated with processing of visual information, we investigated correlations of pareidolia with motor symptoms and striatal dopaminergic function. METHOD: A noise pareidolia test, assessment of motor symptoms using MDS-UPDRS and 123I-Ioflupane SPECT were performed in 58 drug-naïve PD patients. A number of images in which a participant noticed an illusory face (number of illusory responses) were compared with motor assessment scores and uptake of 123I-ioflupane in the striatum. RESULTS: Of the 58 participants, 22 had at least one illusory response. Mean scores for MDS-UPDRS part III (p<0.05), rigidity (p<0.05), and rigidity on the left side of the body (p<0.01) in patients with pareidolia were significantly higher than those in patients without pareidolia. Uptake of 123I-ioflupane in the right caudate nucleus (p<0.05), anterior putamen (p<0.01), and posterior putamen (p<0.01) in patients with pareidolia was significantly lower than in patients without pareidolia. In the 22 patients with pareidolia, the number of illusory responses was significantly correlated with total scores for MDS-UPDRS part III (r=0.443, p<0.05) and subscores for bradykinesia (r=0.440, p<0.05) and bradykinesia on the left side of the body (r=0.564, p<0.01). The prevalence of pareidolia in left-dominant parkinsonism (16/30 patients) was higher than that in right-dominant parkinsonism (6/28 patients) (p<0.05 by chi-square test). CONCLUSION: Pareidolia in PD patients is associated with dysfunction in the right striatum.
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Enfermedad de Parkinson , Preparaciones Farmacéuticas , Cuerpo Estriado/diagnóstico por imagen , Humanos , Hipocinesia , Enfermedad de Parkinson/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
In general, involuntary movements after stroke are due to a disturbance in the unilateral cortico-basal ganglia loop and appear contralateral to stroke lesions. Crossed involuntary movements after unilateral stroke are very rare. We observed a case of crossed involuntary movements in the left upper limb and right lower limb after a right thalamic hemorrhage expanded to the right subthalamic nucleus. We considered a possible three-step theory as the basis of crossed choreoathetosis. This case informs our better understanding of the cortico-basal ganglia loop and involuntary movements after stroke.
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Atetosis/etiología , Corea/etiología , Accidente Cerebrovascular Hemorrágico/complicaciones , Movimiento , Tálamo/irrigación sanguínea , Anciano de 80 o más Años , Atetosis/diagnóstico , Atetosis/fisiopatología , Corea/diagnóstico , Corea/fisiopatología , Accidente Cerebrovascular Hemorrágico/diagnóstico por imagen , Humanos , MasculinoRESUMEN
OBJECTIVES: To investigate the differences in clinical backgrounds, especially weekly variations of stroke occurrence, between hyper-acute ischemic stroke patients with and without regular employment (RE), as well as the impact of RE on outcome. MATERIALS AND METHODS: Symptomatic ischemic stroke patients with ≤4.5 h from onset to door were enrolled. First, we divided patients into the RE and non-RE group to analyze differences in clinical characteristics, especially relation between weekly variations of stroke occurrence and RE. Second, we divided the same patients into those with and without favorable outcomes (modified Rankin Scale score of 0 to 2 at 3 months from stroke onset) to analyze the impact of RE on outcomes. RESULTS: We screened 1,249 consecutive symptomatic ischemic stroke patients and included 377 patients (284 [75%] males; median age, 67 years). Of these patients, 248 (66%) were included in RE group. First, RE was independently associated with occurrence of stroke on Monday in reference to Sunday or a public holiday (OR 2.562, 95% CI 1.004-6.535, p = 0.049). Second, RE (OR 2.888 95% CI 1.378-6.050, p = 0.005) was a factor independently associated with a favorable outcome. CONCLUSIONS: Patients with RE were more likely to have a hyper-acute ischemic stroke on Monday in reference to Sunday or a public holiday. However, RE before stroke onset appears to have a positive impact on outcome.
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Empleo , Accidente Cerebrovascular Isquémico/epidemiología , Estrés Laboral/epidemiología , Determinantes Sociales de la Salud , Anciano , Anciano de 80 o más Años , Evaluación de la Discapacidad , Femenino , Estado Funcional , Humanos , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/terapia , Masculino , Persona de Mediana Edad , Estrés Laboral/diagnóstico , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores Socioeconómicos , Factores de TiempoRESUMEN
INTRODUCTION AND OBJECTIVES: The clinical characteristics of convexity subarachnoid hemorrhage (cSAH) accompanying hyperacute ischemic stroke are unknown. We aimed to investigate the incidence and clinical characteristics of cSAH with hyperacute ischemic stroke. METHODS: Participants comprised symptomatic ischemic stroke patients with ≤4.5 h from onset to door who also underwent initial MRI ≤4.5 h from onset. We reviewed initial and follow-up MRI during admission to identify cSAH. Retrospective reviews of cSAH incidence and clinical characteristics were performed. RESULTS: We screened 1,249 consecutive symptomatic ischemic stroke patients, including 384 patients (279 males [73%]; median age, 67 years). Of the 384 patients, arterial ischemic stroke was seen in 382 patients, and venous ischemic stroke in 2 patients. Of the hyperacute arterial ischemic stroke, cSAH was identified within 4.5 h of ischemic stroke onset in 2 patients (0.5%) and around 6 days from ischemic stroke onset in 2 patients (0.5%). Of the hyperacute venous ischemic stroke, cSAH was observed in 1 patient on initial MRI. Comparing the clinical characteristics of hyperacute arterial ischemic stroke with and without cSAH, patients with cSAH were more likely to have arterial stenosis or occlusion ipsilateral to the cSAH (100 vs. 47%, p = 0.048), and the ischemic lesion only in the right hemisphere (100 vs. 33%, p = 0.013). In all cases, outcomes were favorable (modified Rankin Scale 0-1 at 3 months from onset). CONCLUSIONS: Convexity SAH was observed in 0.5% of hyperacute ischemic patients within 4.5 h of ischemic stroke onset and in 0.5% around 6 days from ischemic stroke onset.
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Isquemia Encefálica/epidemiología , Accidente Cerebrovascular/epidemiología , Hemorragia Subaracnoidea/epidemiología , Adulto , Anciano , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/fisiopatología , Angiografía Cerebral , Circulación Cerebrovascular , Circulación Colateral , Bases de Datos Factuales , Evaluación de la Discapacidad , Femenino , Humanos , Incidencia , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pronóstico , Sistema de Registros , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/fisiopatología , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/fisiopatología , Factores de Tiempo , Tokio/epidemiologíaRESUMEN
PURPOSE: Sympathetic nervous denervation may be associated with the development of anemia. We aimed to investigate the association between sympathetic nervous denervation and hemoglobin levels in patients with Parkinson's disease (PD). METHODS: As indices of sympathetic nervous denervation, we investigated resting norepinephrine levels, increased norepinephrine levels after tilt-up, cardiac uptake of 123I-metaiodobenzylguanidine, supine blood pressure, and the degree of orthostatic hypotension in 132 patients with de novo PD. RESULTS: Older age, female sex, severe motor dysfunction, and lower body mass index were associated with decreased hemoglobin levels. After adjustment for these covariables, resting norepinephrine levels were negatively associated with hemoglobin levels. Hemoglobin levels were not associated with cardiac sympathetic denervation or orthostatic intolerance. CONCLUSION: Hemoglobin levels in PD seem to be closely related to noradrenergic nervous activity and nigrostriatal dopaminergic degeneration. In contrast to expectations, decreased hemoglobin levels were associated with increased whole-body sympathetic nervous activity in PD.
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Hipotensión Ortostática , Enfermedad de Parkinson , 3-Yodobencilguanidina , Anciano , Femenino , Hemoglobinas , Humanos , Sistema Nervioso SimpáticoRESUMEN
BACKGROUND: Depression is a symptom of Parkinson's disease (PD) and may be correlated with cardiovascular sympathetic function. Anhedonia is an element of depression, but these symptoms can emerge independently in PD. A correlation of anhedonia with cardiovascular sympathetic function has rarely been examined. OBJECTIVE: To compare correlations of depression and anhedonia with cardiovascular sympathetic function in drug-naive PD patients. METHODS: Assessments of depression (Self-rating Depression Scale; SDS), anhedonia (Snaith-Hamilton Pleasure Scale; SHAPS), myocardial 123I-MIBG (123I-meta-iodobenzylguanidine) scintigraphy (heart to mediastinum (H/M) ratios in early and delayed images), and head-up tilt test (HUT) up to 60° for 10 min were performed in 45 drug-naïve PD patients. During the HUT, blood pressure was measured every minute and the maximum decrease in systolic blood pressure (SBP) was determined. Plasma noradrenaline (NA) and arginine vasopressin (AVP) levels were examined at baseline and 10 min after tilt, with subsequent calculation of increases in plasma NA and AVP levels in this 10 min. Correlation coefficients were calculated among these assessment parameters. RESULTS: SDS significantly correlated with % maximum decrease in SBP (r = 0.344, p = 0.02), but not with H/M ratios in both images and increases in plasma NA and AVP levels. SHAPS did not correlate with the change in SBP, H/M ratios in both images, or plasma NA and AVP levels. CONCLUSION: Depression was correlated with the % maximum decrease in SBP during a 10-min HUT, but anhedonia did not show this relationship. This suggests that depression and anhedonia may have different pathophysiological backgrounds in drug-naïve PD patients.
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Enfermedad de Parkinson , Preparaciones Farmacéuticas , 3-Yodobencilguanidina , Anhedonia , Depresión/diagnóstico por imagen , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagenRESUMEN
BACKGROUND AND AIM: Toxic oligomeric α-synuclein (αS; O-αS) has been suggested to play a central role in the pathogenesis of Lewy body diseases such as Parkinson's disease (PD). Cerebrospinal fluid (CSF) levels of αS, O-αS, total and phosphorylated tau, and amyloid ß 1-42 (Aß1-42) are thought to reflect the pathophysiology or clinical symptoms in PD. In this study, we examined correlations of the CSF levels of these proteins with the clinical symptoms, and with each other in drug-naïve patients with PD. METHODS: Twenty-seven drug-naïve patients with PD were included. Motor and cognitive functions were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment (MoCA), and Neurobehavioral Cognitive Status Examination (COGNISTAT). CSF levels of total αS, O-αS, Aß1-42, total tau and tau phosphorylated at threonine 181 (P-tau181p) were measured. CSF levels of these proteins were compared with clinical assessments from the UPDRS, MoCA and COGNISTAT using Spearman correlation analysis. Spearman correlation coefficients among CSF protein levels were also evaluated. RESULTS: CSF levels of αS were negatively correlated with UPDRS part III (motor score) (p < 0.05) and bradykinesia (p < 0.01), and positively correlated with COGNISTAT subtest of judgement (p < 0.01) and CSF levels of Aß1-42 (p < 0.001), total tau (p < 0.001) and P-tau181p (p < 0.01). Lower CSF levels of Aß1-42, total tau and P-tau181p were significantly related to worsening of some motor and/or cognitive functions. The CSF level of O-αS showed no correlation with any motor and cognitive assessments or with CSF levels of the other proteins. CONCLUSION: CSF levels of αS are correlated with some clinical symptoms and CSF levels of other pathogenic proteins in drug-naïve PD patients. These correlations suggest a central role for interaction and aggregation of αS with Aß1-42, tau, and phosphorylated tau in the pathogenesis of PD. Although O-αS has been shown to have neurotoxic effects, CSF levels do not reflect clinical symptoms or levels of other proteins in cross-sectional assessment.
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Péptidos beta-Amiloides/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Enfermedad de Parkinson/líquido cefalorraquídeo , alfa-Sinucleína/líquido cefalorraquídeo , Proteínas tau/líquido cefalorraquídeo , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/fisiopatologíaRESUMEN
PURPOSE: The aim of this multicenter trial was to generate a [123I]FP-CIT SPECT database of healthy controls from the common SPECT systems available in Japan. METHODS: This study included 510 sets of SPECT data from 256 healthy controls (116 men and 140 women; age range, 30-83 years) acquired from eight different centers. Images were reconstructed without attenuation or scatter correction (NOACNOSC), with only attenuation correction using the Chang method (ChangACNOSC) or X-ray CT (CTACNOSC), and with both scatter and attenuation correction using the Chang method (ChangACSC) or X-ray CT (CTACSC). These SPECT images were analyzed using the Southampton method. The outcome measure was the specific binding ratio (SBR) in the striatum. These striatal SBRs were calibrated from prior experiments using a striatal phantom. RESULTS: The original SBRs gradually decreased in the order of ChangACSC, CTACSC, ChangACNOSC, CTACNOSC, and NOACNOSC. The SBRs for NOACNOSC were 46% lower than those for ChangACSC. In contrast, the calibrated SBRs were almost equal under no scatter correction (NOSC) conditions. A significant effect of age was found, with an SBR decline rate of 6.3% per decade. In the 30-39 age group, SBRs were 12.2% higher in women than in men, but this increase declined with age and was absent in the 70-79 age group. CONCLUSIONS: This study provided a large-scale quantitative database of [123I]FP-CIT SPECT scans from different scanners in healthy controls across a wide age range and with balanced sex representation. The phantom calibration effectively harmonizes SPECT data from different SPECT systems under NOSC conditions. The data collected in this study may serve as a reference database.
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Tomografía Computarizada de Emisión de Fotón Único , Tropanos , Adulto , Anciano , Anciano de 80 o más Años , Niño , Bases de Datos Factuales , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Fantasmas de ImagenRESUMEN
We examined the correlations between cerebrospinal fluid (CSF) concentrations of homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) and imaging assessment scores, using 123I-Ioflupane SPECT and 123I-MIBG myocardial scintigraphy in 23 drug naïve PD patients. The CSF 5-HIAA concentration correlated with the H/M ratio of the delayed image (r = 0.458, p < 0.05) and the washout rate (r = - 0.642, p < 0.01) of 123I-MIBG myocardial scintigraphy. These correlations suggest some unclarified pathophysiological links between the central serotonergic and cardiac sympathetic systems.
Asunto(s)
3-Yodobencilguanidina/farmacocinética , Ácido Hidroxiindolacético/líquido cefalorraquídeo , Radioisótopos de Yodo/farmacocinética , Imagen de Perfusión Miocárdica , Miocardio/metabolismo , Nortropanos/farmacocinética , Enfermedad de Parkinson/metabolismo , Radiofármacos/farmacocinética , Tomografía Computarizada de Emisión de Fotón Único , Anciano , Anciano de 80 o más Años , Fibras Autónomas Posganglionares/metabolismo , Biomarcadores , Disfunción Cognitiva/etiología , Demencia/etiología , Femenino , Sistema de Conducción Cardíaco/fisiopatología , Ácido Homovanílico/líquido cefalorraquídeo , Humanos , Masculino , Persona de Mediana Edad , Especificidad de Órganos , Enfermedad de Parkinson/líquido cefalorraquídeo , Enfermedad de Parkinson/psicología , Serotonina/metabolismoRESUMEN
BACKGROUNDS: It is often difficult to diagnose stroke subtypes at admission, particularly in sinus rhythm cases. Vascular pedicle width (VPW) on chest X-ray (CXR) and maximal P-wave duration (P-max) on electrocardiogram (ECG) are again realized as useful parameters reflecting intravascular volume and atrial conduction status, respectively. We investigated the utility of VPW and P-max as a tool for differentiating ischemic stroke subtypes. METHODS: We studied 343 acute stroke patients showing sinus rhythm on admission. Dividing the patients into cardioembolic (CE) stroke (n = 57) and non-CE (n = 286) groups, we compared clinical backgrounds including VPW on CXR, and P-max in lead II and premature atrial contraction (PAC) on 12-leads ECG. Then, we investigated the independent factors for CE. RESULTS: Independent factors associated with CE were VPW (≥59.3 mm) (p < 0.001; odds ratio (OR), 10.12; 95% confidence interval (CI), 4.13-24.8), P-max in lead II (≥120 ms) (p < 0.001; OR, 8.61; 95% CI, 3.96-18.7), PAC (p = 0.002; OR, 7.35; 95% CI, 2.14-25.3) and D-dimer level (≥1.11 µg/ml) (p = 0.016; OR, 2.57; 95% CI, 1.20-5.51). CONCLUSIONS: VPW, P-max, PAC and D-dimer are useful parameters for diagnosing CE stroke in patients with sinus rhythm at admission.