RESUMEN
VPS35 plays a key role in neurodegenerative processes in Alzheimer's disease and Parkinson's disease (PD). Many genetic studies have shown a close relationship between autophagy and PD pathophysiology, and specifically, the PD-causing D620N mutation in VPS35 has been shown to impair autophagy. However, the molecular mechanisms underlying neuronal cell death and impaired autophagy in PD are debated. Notably, increasing evidence suggests that Rab9-dependent "alternative" autophagy, which is driven by a different molecular mechanism that driving ATG5-dependent "conventional" autophagy, also contributes to neurodegenerative process. In this study, we investigated the relationship between alternative autophagy and VPS35 D620N mutant-related PD pathogenesis. We isolated iPSCs from the blood mononuclear cell population of two PD patients carrying the VPS35 D620N mutant. In addition, we used CRISPR-Cas9 to generate SH-SY5Y cells carrying the D620N variant of VPS35. We first revealed that the number of autophagic vacuoles was significantly decreased in ATG5-knockout Mouse Embryonic Fibroblast or ATG5-knockdown patient-derived dopaminergic neurons carrying the VPS35 D620N mutant compared with that of the wild type VPS35 control cells. Furthermore, estrogen, which activates alternative autophagy pathways, increased the number of autophagic vacuoles in ATG5-knockdown VPS35 D620N mutant dopaminergic neurons. Estrogen induces Rab9 phosphorylation, mediated through Ulk1 phosphorylation, ultimately regulating alternative autophagy. Moreover, estrogen reduced the apoptosis rate of VPS35 D620N neurons, and this effect of estrogen was diminished under alternative autophagy knockdown conditions. In conclusion, alternative autophagy might be important for maintaining neuronal homeostasis and may be associated with the neuroprotective effect of estrogen in PD with VPS35 D620N.
Asunto(s)
Neuroblastoma , Enfermedad de Parkinson , Animales , Humanos , Ratones , Autofagia/genética , Neuronas Dopaminérgicas/metabolismo , Estrógenos/farmacología , Estrógenos/metabolismo , Fibroblastos/metabolismo , Mutación/genética , Neuroblastoma/metabolismo , Enfermedad de Parkinson/patología , Transporte de Proteínas , Proteínas de Transporte Vesicular/metabolismoRESUMEN
INTRODUCTION: Many guidelines now recommend early rehabilitation for acute stroke patients. However, evidence remains lacking regarding the specific timings for initiation of various rehabilitation steps and management when complications are encountered in acute stroke rehabilitation. This survey aimed to investigate actual clinical situations in acute stroke rehabilitation in Japan and to improve the medical systems for rehabilitation and plan further studies. METHODS: This nationwide, cross-sectional, web-based questionnaire survey was administered between February 7, 2022, and April 21, 2022, targeting all primary stroke centers (PSCs) in Japan. Among several components of the survey, this paper focused on the timing of the initiation of three rehabilitation steps (passive bed exercise; head elevation; and out-of-bed mobilization), along with the management of rehabilitation (continued or suspended) in the event of complications during acute stroke rehabilitation. We also investigated the influence of facility features on these contents. RESULTS: Responses were obtained from 639 of the 959 PSCs surveyed (response rate: 66.6%). In cases of ischemic stroke and intracerebral hemorrhage, most PSCs initiated passive bed exercise on day 1, head elevation on day 1, and out-of-bed mobilization on day 2 (with day of admission defined as day 1). In cases with subarachnoid hemorrhage, rehabilitation steps were delayed compared to other stroke subtypes or showed wide variation depending on the facility. Passive bed exercise was accelerated by the presence of protocols for rehabilitation and weekend rehabilitation. Out-of-bed mobilization was accelerated by the presence of a stroke care unit. Facilities with board-certified rehabilitation doctors were cautious regarding the initiation of head elevation. Most PSCs suspended rehabilitation training in the event of symptomatic systemic/neurological complications. CONCLUSION: Our survey revealed the actual situation of acute stroke rehabilitation in Japan and indicated that some facility features appear to influence early increases in physical activity levels and early mobilization. Our survey provides fundamental data to improve the medical systems for acute stroke rehabilitation in the future.
Asunto(s)
Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Japón , Estudios Transversales , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapia , Encuestas y Cuestionarios , InternetRESUMEN
BACKGROUND: The AmplatzerTM PFO Occluder was approved for marketing in Japan in May 2019, and the Amplatzer PFO Occluder Japan Post-marketing Surveillance (PFO Japan PMS) study was initiated in December 2019. This analysis presents 30-day clinical outcomes for PFO Japan PMS study patients. METHODS AND RESULTS: PFO Japan PMS is a prospective single-arm non-randomized multicenter clinical study. Eligible patients were indicated for patent foramen ovale (PFO) closure and underwent an implant attempt with the AmplatzerTM PFO Occluder. Technical success was defined as successful delivery and release of the occluder; procedural success was defined as technical success with no serious adverse events (SAEs) within 1 day of the procedure. The primary safety endpoint includes predefined device- and/or procedure-related SAEs through 30 days after the procedure. From December 2019 to July 2021, 500 patients were enrolled across 53 Japanese sites. The mean (±SD) patient age was 52.7±15.4 years, and 29.8% of patients were aged >60 years. Technical and procedural success rates were both high (99.8% and 98.8%, respectively). Further, there was only one primary safety endpoint event (0.2%): an episode of asymptomatic paroxysmal atrial fibrillation that occurred 26 days after the procedure. CONCLUSIONS: In this real-world Japanese study with almost one-third of patients aged >60 years, PFO closure with the AmplatzerTM PFO Occluder was performed successfully and safely, with a low incidence of procedure-related atrial arrhythmias.
Asunto(s)
Foramen Oval Permeable , Vigilancia de Productos Comercializados , Dispositivo Oclusor Septal , Humanos , Foramen Oval Permeable/cirugía , Japón , Persona de Mediana Edad , Masculino , Femenino , Adulto , Anciano , Dispositivo Oclusor Septal/efectos adversos , Estudios Prospectivos , Resultado del Tratamiento , Cateterismo Cardíaco/efectos adversos , Cateterismo Cardíaco/instrumentación , Factores de TiempoRESUMEN
BACKGROUND AND AIMS: Small ischemic lesions (SILs) accompanying intracerebral hemorrhage (ICH) might be induced by small-vessel vulnerability and hypercoagulation. Some polyunsaturated fatty acids (PUFAs) have been associated with hypercoagulation in cardiovascular diseases. Our aim here is to determine how pre-existing small-vessel disease (SVD) and PUFAs may affect SILs. METHODS AND RESULTS: We screened consecutive ICH patients (October 2012-December 2021) meeting two inclusion criteria: (1) the patients were hospitalized for acute ICH and were undergoing magnetic resonance imaging and (2) the patients' PUFA measurements were available. After excluding patients with isolated intraventricular hemorrhage, we evaluated whether three SVD markers (white matter hyperintensities, old lacunes, cerebral microbleeds) and PUFAs might be associated with the development of SILs. We selected 319 participants from 377 screened consecutive ICH patients (median age = 64, males = 207 [65 %]). Of the 319 patients, 45 patients (14 %) developed SILs. In a multivariable logistic regression analysis, the factors associated with SILs were old lacunes (OR 3.255, 95 % CI 1.101-9.622, p = 0.033) and DHA/AA ratio (OR 0.180, 95 % CI 0.046-0.704, p = 0.013). Furthermore, in our multivariable analysis using DHA/AA ratio tertiles with and without SILs, we observed a linear trend between SILs and the Higher Tertile of the DHA/AA ratio (DHA/AA ratio Mid-Tertile: OR 1.330, 95%CI 0.557-3.177, p = 0.521, and DHA/AA ratio Lower Tertile: OR 2.632, 95%CI 1.124-6.162, p = 0.026). CONCLUSION: The presence of old lacunes and lower DHA/AA ratios might be associated with SILs accompanying ICH.
Asunto(s)
Enfermedades de los Pequeños Vasos Cerebrales , Masculino , Humanos , Persona de Mediana Edad , Hemorragia Cerebral/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Ácidos Grasos InsaturadosRESUMEN
INTRODUCTION: Acute stroke rehabilitation is crucial for achieving good functional recovery, even during the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to clarify the impact of the COVID-19 pandemic on acute stroke rehabilitation and identify which components in the acute stroke rehabilitation provision system were susceptible to the pandemic. METHODS: A web-based questionnaire survey was conducted in all primary stroke centers (PSCs) in Japan between February 7 and April 21, 2022. The survey included questions about the current status of acute stroke rehabilitation and the influence of the pandemic. We classified the influences and investigated the relationship between the influence of the pandemic and the provision of rehabilitation. Additionally, we investigated a group of prefectures divided according to the grade of the pandemic. RESULTS: The survey response rate was 67% (639 of 959 PSCs). Among them, 387 PSCs (61%) reported that the COVID-19 pandemic affected acute stroke rehabilitation. In PSCs affected by the pandemic, more rehabilitation-related staff were working, and the proportion of weekend/holiday rehabilitation implementation was higher compared to those unaffected. In PSCs from highly infected prefectures, no significant relationship was observed between the influence of the pandemic and the rehabilitation provision system. CONCLUSIONS: PSCs that provide denser acute stroke rehabilitation may be affected to a greater extent by the pandemic. We conclude that stroke hospitals should formulate infection control procedures for acute stroke rehabilitation in advance, depending on the conditions of the region and facility.
RESUMEN
BACKGROUND AND PURPOSE: The impact of CHADS2 score on outcome in patients with stroke taking an oral anticoagulant (OAC) has not yet been fully elucidated. We investigated the association between pre-stroke CHADS2 score and outcome at discharge in patients with acute cardioembolic (CE) stroke due to atrial fibrillation (AF) who were prescribed OAC. METHODS: The data of 548 OAC-treated patients with AF and CE stroke who were registered in the multicenter Prospective Analysis of Stroke patients Taking oral Anticoagulants (PASTA) study were analyzed. High CHADS2 score was defined as a pre-stroke CHADS2 score ≥2. Unfavorable outcome was defined as a modified Rankin scale (mRS) of 3-6. The impacts of pre-stroke CHADS2 score on outcome at discharge were evaluated using multiple logistic regression analysis. RESULT: A high CHADS2 score was found in 472/548 patients and unfavorable outcome was found in 330/548 patients. In patients with unfavorable outcome, age, male sex, pre-stroke CHADS2 score, initial National Institute Health Stroke Scale (NIHSS) score, and glucose level on admission were significantly higher, whereas creatinine clearance and body weight were significantly lower, than those with favorable outcome (each p < 0.001). Multivariate logistic regression analysis indicated that high CHADS2 score (OR 2.18, 95 %CI 1.08-4.42, p = 0.031), pre-stroke mRS (OR 2.21, 95 %CI 1.69-2.67, p < 0.001), and initial NIHSS score (OR 1.19, 95 %CI 1.17-1.24, p < 0.001) were independently associated with unfavorable outcome. CONCLUSION: Pre-stroke CHADS2 score was associated with poor outcome in patients with cardioembolic stroke due to AF, even in those taking OAC.
Asunto(s)
Fibrilación Atrial , Accidente Cerebrovascular Embólico , Accidente Cerebrovascular , Humanos , Masculino , Accidente Cerebrovascular Embólico/complicaciones , Factores de Riesgo , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/etiología , Anticoagulantes/efectos adversos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Sistema de RegistrosRESUMEN
OBJECTIVES: The early initiation of acute stroke rehabilitation with a sufficient dose, including at weekends/holidays, is important to improve functional outcome. We investigated the status of acute stroke rehabilitation in Japan by using a nationwide survey. MATERIALS AND METHODS: Facility features, rehabilitation dose provided in the first week in each stroke subtype, and weekend/holiday rehabilitation were investigated by using the results of a web-based survey among primary stroke centers. The relationships between facility features and weekend/holiday rehabilitation were also analyzed. RESULTS: A total of 639 stroke centers (66.6%) completed the questionnaire. The overall median dose was 2.0 (interquartile range, 1.7-3.0) U/day (1U = 20 min). After 7 days, the overall median dose increased to 4.0 (2.0-5.4) U/day. Almost 50% of facilities replied that they could not provide a sufficient dose of rehabilitation; the main reason was a lack of therapists (31%). For rehabilitation on long weekends, no rehabilitation was provided on 3-day weekends in 19% of facilities, and in 5% of facilities on ≥4-day weekends. The mean number of therapists was almost 50% less in the facilities that provided no rehabilitation on 3-day weekends compared to those that provided daily rehabilitation (19.4 vs. 36.2 therapists, respectively, p < 0.001). CONCLUSIONS: In this survey, the provision of acute stroke rehabilitation, including non-working days, was clarified. According to the results, prospective interventional or observational studies are needed to design more effective rehabilitation programs to improve outcome. In particular, it is important to determine the optimal dose and intensity of acute stroke rehabilitation.
Asunto(s)
Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Vacaciones y Feriados , Estudios Prospectivos , Japón , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapia , Encuestas y CuestionariosRESUMEN
OBJECTIVES: Heart failure may result in reduced brain perfusion, limiting the blood flow needed to achieve clinical recovery. We investigated whether plasma levels of brain natriuretic peptide (BNP), a biological marker of heart failure, were related to clinical outcomes after mechanical thrombectomy (MT). MATERIALS AND METHODS: Data were analyzed from stroke patients with internal carotid or middle cerebral artery occlusion enrolled in the SKIP trial for whom plasma level of BNP was evaluated on admission. Favorable outcome was defined as a modified Rankin scale score of 0-2 at 3 months. RESULTS: Among 169 patients (median age, 74 years; 62% men, median National Institutes of Health Stroke Scale score, 18), 104 (62%) achieved favorable outcomes. Median plasma BNP level was lower in the favorable outcome group (124.1 pg/mL; interquartile range [IQR], 62.1-215.5 pg/mL) than in the unfavorable outcome group (198.0 pg/mL; IQR, 74.8-334.0 pg/mL; p=0.005). In multivariate regression analysis, the adjusted odds ratio for BNP for favorable outcomes was 0.971 (95% confidence interval, 0.993-0.999; p=0.048). At 3 months after onset, the favorable outcome rate was lower in the ≥186 pg/mL group (45%) than in the <186 pg/mL group (72%; p=0.001). This significant difference remained regardless of the presence of atrial fibrillation (AF), with rates of 47% and 76%, respectively, in AF patients (p=0.003) and 33% and 68%, respectively, in patients without AF (p=0.046). CONCLUSION: High plasma BNP concentration appears associated with unfavorable outcomes after MT.
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.
Asunto(s)
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.
Asunto(s)
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
Eculizumab, a humanized monoclonal antibody, is a complement inhibitor indicated for refractory generalized myasthenia gravis (MG). However, there are limited data on the safety of eculizumab for MG during coronavirus disease 2019 (COVID-19) infection. We report a case in which eculizumab was continued for MG after contracting COVID-19, followed by a favorable outcome.
Asunto(s)
COVID-19 , Miastenia Gravis , Anticuerpos Monoclonales Humanizados/uso terapéutico , Inactivadores del Complemento/uso terapéutico , Humanos , Miastenia Gravis/complicaciones , Miastenia Gravis/tratamiento farmacológicoRESUMEN
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.
Asunto(s)
Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/psicología , Cognición , Arginina , LisinaRESUMEN
Steal syndrome is a vascular disorder characterized by the inappropriate alterations of blood flow through adjacent collateral blood vessels to compensate for ischemia in organs with severely reduced or lost blood flow. The result may lead to dysfunction or ischemia of the end organs supplied by the collateral vessels. A 76-year-old man presented with a recurring, transient right-sided amaurosis that lasted about 30 min when drinking and mastication during meals. Carotid ultrasound and angiography showed severe stenosis of the right common carotid artery, and retrograde flow of the right external carotid artery via a collateral branch from the right vertebral artery. After drinking and mastication, steal syndrome from the right internal carotid artery to the external carotid artery were observed in real time by ultrasound. After percutaneous angioplasty for stenosis, the anastomosis from the vertebral artery to the external carotid artery, and the retrograde flow of the external carotid artery disappeared, and amaurosis improved during mastication and drinking. We found that drinking and mastication caused a phenomenon of blood theft from the internal carotid artery to the external carotid artery in common carotid artery stenosis. It is important to recognize the clinical presentation of these patients, because this condition is potentially reversible once identified with a proper evaluation and appropriate surgical intervention applied.
Asunto(s)
Arteria Carótida Externa , Masticación , Anciano , Ceguera , Arteria Carótida Externa/cirugía , Arteria Carótida Interna/diagnóstico por imagen , Constricción Patológica/complicaciones , Humanos , Isquemia , MasculinoRESUMEN
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.
Asunto(s)
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
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.
Asunto(s)
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.
Asunto(s)
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.
Asunto(s)
Hipotensión Ortostática , Enfermedad de Parkinson , Presión Sanguínea , Frecuencia Cardíaca , Humanos , Hipotensión Ortostática/etiología , Enfermedad de Parkinson/complicaciones , Pruebas de Mesa InclinadaRESUMEN
BACKGROUND AND OBJECTIVES: Communication-type medical smartphone applications enable text, neuroimaging, photos, and videos to be shared securely among the stroke team. Our aim was to investigate whether use of a smartphone application would shorten the duration from admission to reperfusion therapy in patients with hyper-acute ischemic stroke. METHODS: Enrolled were acute ischemic stroke patients who underwent reperfusion therapy (intravenous tissue plasminogen activator (IV t-PA) and mechanical thrombectomy (MT)) at our hospital between October 2012 and September 2018. We divided the patients into two groups based on the date of availability on smartphones of communication-type medical application: (1) Control group, conventional communication prior to September 2015, and (2) App group, communication via the smartphone app from October 2015 onwards. We compared door-to-image time (DIT), image-to-needle time (INT), door-to-needle time (DNT) for thrombolysis, and DIT, image-to-puncture time (IPT), and door-to-puncture time (DTP) for thrombectomy between the groups. RESULTS: We retrospectively enrolled 139 patients (68% male; median age, 69 years; median NIHSS score, 7) who were assigned into the App group (n = 86) and Control group (n = 53). Of the overall patients, 109 underwent IV t-PA (IV t-PA alone, 79 patients), and 63 underwent MT (MT alone, 30 patients), and 33 patients underwent combined IV t-PA and MT. There was no significant difference in DIT between the App and Control groups (23 min vs. 22 min, p = 0.493). DNT, DPT, INT, and IPT were significantly shorter in the App group than in the Control group (DNT, 62 min for the App group vs. 72 min for Control group, p = 0.038; INT, 42 vs. 48 min, p = 0.009; DPT, 106 vs. 129 min, p = 0.046; IPT, 89 vs. 117 min, p = 0.004). CONCLUSION: The present findings indicate that communication-type medical smartphone apps have potential for shortening the time elapsed between admission and reperfusion therapy, especially INT and IPT.
Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular , Anciano , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/terapia , Comunicación , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Masculino , Reperfusión , Estudios Retrospectivos , Teléfono Inteligente , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/tratamiento farmacológico , Trombectomía , Terapia Trombolítica , Activador de Tejido Plasminógeno/uso terapéutico , Resultado del TratamientoRESUMEN
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.
Asunto(s)
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
BACKGROUND: Telestroke has developed rapidly as an assessment tool for patients eligible for reperfusion therapy. OBJECTIVE: To investigate whether vascular neurologists can diagnose intracranial large vessel occlusion (LVO) as quickly and accurately using a smartphone application compared to a hospital-based desktop PC monitor. METHODS: We retrospectively enrolled 108 consecutive patients with acute ischemic stroke in the middle cerebral artery territory who underwent magnetic resonance imaging (MRI) within 24 hours of their stroke onset. Two vascular neurologists, blinded to all clinical information, independently evaluated magnetic resonance angiography and fluid-attenuated inversion recovery images for the presence or absence of LVO in the internal carotid artery and middle cerebral artery (M1, M2, or M3) on both a smartphone application (Smartphone-LVO) and a hospital-based desktop PC monitor (PC-LVO). To evaluate the accuracy of an arterial occlusion diagnosis, interdevice variability between Smartphone-LVO and PC-LVO was analyzed using κ statistics, and image interpretation time was compared between Smartphone-LVO and PC-LVO. RESULTS: There was broad agreement between Smartphone-LVO and PC-LVO evaluations regarding the presence or absence of arterial occlusion (Reader 1: κ=0.94; P<.001 vs Reader 2: κ=0.89; P<.001), and interpretation times were similar between Smartphone-LVO and PC-LVO. CONCLUSIONS: The results indicate the evaluation of neuroimages using a smartphone application can provide an accurate and timely diagnosis of anterior intracranial arterial occlusion that can be shared immediately with members of the stroke team to support the management of patients with hyperacute ischemic stroke.