Nilotinib treatment outcomes in autosomal dominant spinocerebellar ataxia over one year.

We evaluated the efficacy and safety of 1-year treatment with nilotinib (Tasigna®) in patients with autosomal dominant spinocerebellar ataxia (ADSCA) and the factors associated with responsiveness. From an institutional cohort, patients with ADSCA who completed a 1-year treatment with nilotinib (150-300 mg/day) were included. Ataxia severity was assessed using the Scale for the Rating and Assessment of Ataxia (SARA), scores at baseline and 1, 3, 6, and 12 months. A subject was categorized 'responsive' when the SARA score reduction at 12 M was > 0. Pretreatment serum proteomic analysis included subjects with the highest (n = 5) and lowest (n = 5) SARA score change at 12 months and five non-ataxia controls. Thirty-two subjects (18 [56.2%] females, median age 42 [30-49.5] years) were included. Although SARA score at 12 M did not significantly improve in overall population, 20 (62.5%) subjects were categorized as responsive. Serum proteomic analysis identified 4 differentially expressed proteins, leucine-rich alpha-2-glycoprotein (LRG1), vitamin-D binding protein (DBP), and C4b-binding protein (C4BP) beta and alpha chain, which are involved in the autophagy process. This preliminary data suggests that nilotinib might improve ataxia severity in some patients with ADSCA. Serum protein markers might be a clue to predict the response to nilotinib.Trial Registration Information: Effect of Nilotinib in Cerebellar Ataxia Patients (NCT03932669, date of submission 01/05/2019).

Association between depression and young-onset dementia in middle-aged women.

BACKGROUND: Dementia is associated with older adults; however, it can also affect younger individuals, known as young-onset dementia (YOD), when diagnosed before the age of 65 years. We aimed to conduct a retrospective cohort study involving middle-aged women to investigate the association between premorbid depression and YOD development. METHODS: We included 1.6 million women aged 40-60 years who underwent health checkups under the Korean National Health Insurance Service and investigated the association between depression and YOD. RESULTS: Women with depression had a significantly higher risk of developing YOD than women without depression. Among premenopausal women, those with depression had a 2.67-fold increased risk, whereas postmenopausal women with depression had a 2.50-fold increased risk. Late age at menarche (> 16 years) and young age at menopause (< 40 years) was associated with an increased risk of YOD. CONCLUSIONS: Depression in middle-aged women is a significant risk factor for the development of YOD. Understanding the role of reproductive factors can aid in the development of targeted therapeutic interventions to prevent or delay YOD.

Understanding epileptogenesis from molecules to network alteration.

Epilepsy is characterized by recurrent seizures. Following an initial insult, a latent period precedes the onset of spontaneous seizures, a process referred to as epileptogenesis. This period plays a critical role in halting the progression toward epilepsy before the onset of abnormal molecular and network alterations. In this study, the fundamental concepts of epileptogenesis as well as the associated molecular and cellular targets are reviewed.

Clinical and diagnostic characteristics of Hashimoto's encephalopathy: a single-center, retrospective study.

BACKGROUND AND PURPOSE: Diagnosing Hashimoto's encephalopathy (HE) is challenging. In contrast to other types of autoimmune encephalitis, HE shows an excellent response to steroid treatment. We aimed to investigate the rates of antithyroid antibodies (ATAs) and probable HE in patients with unexplained mental dysfunction and compare the clinical characteristics between the good- and poor-outcome groups. METHODS: We retrospectively reviewed the medical records and electroencephalography (EEG) and neuroimaging findings of patients admitted to the Department of Neurology of our hospital from March 1, 2006, to February 28, 2023. Using our proposed diagnostic criteria for probable HE, we compared the clinical characteristics between the good- and poor-outcome groups. We also investigated the rates of ATA positivity and probable HE. RESULTS: In total, 198 patients exhibited altered mentation, rapidly progressive cognitive decline, or myoclonus. ATA tests were performed on 86 patients, and the detection rates of ATAs and probable HE were 29.1% and 25.6%, respectively. Of the 22 patients enrolled, the good- and poor-outcome groups comprised 19 and 3 patients, respectively. Clinical seizures occurred in seven patients. Nonconvulsive status epilepticus on EEG was observed in six patients, all of whom were intractable to antiepileptic drugs. Nineteen of 21 patients (90.5%) treated with immunosuppressants showed good outcomes. CONCLUSIONS: HE is a rare clinical disorder, but not as rare as previously thought. When HE is suspected, steroids should be considered the first-line treatment. Early diagnosis and adequate treatment are critical to achieve good outcomes in HE.

The relationship between sleep and innate immunity.

Sleep regulates inflammatory responses, and the innate immune system affects sleep. Interleukin-1 beta, tumor necrosis factor alpha, growth hormone-releasing hormone, prolactin, and nitric oxide are somnogenic substances. Sleep deprivation, such as chronic insomnia or obstructive sleep apnea, affects cytokine production, glial function, natural killer cell activity, and inflammasome function. This review will discuss the relationship between sleep and innate immunity.

First report of Perkinsus marinus occurrence associated with wild Pacific oysters Crassostrea gigas from the west coast of Korea.

This study reports the occurrence of Perkinsus marinus associated with wild Pacific oyster (Crassostrea gigas) specimens collected along the west coast of Korea. Confirmation of P. marinus presence was achieved by conventional PCR using World Organization of Animal Health (WOAH)-recommended primers that specifically targeted regions of the rDNA locus (ITS1, 5.8S, and ITS2). Sequencing of 10 samples revealed two distinct sequences differing by a single base pair, indicating potential haplotype variability. One sequence closely resembled the P. marinus strain found in Maryland, USA, whereas the other exhibited divergence, indicative of species diversity in the Korean strain, as was evident from the haplotype network analysis. Further validation involved the Ray's Fluid Thioglycollate Medium (RFTM) assay, which initially yielded inconclusive results, possibly due to low infection intensity. Subsequently, RFTM and 2 M NaOH assays conducted on the isolates in the present study, cultured P. marinus cells in standard DMEM/F12 medium, and a positive P. marinus strain (ATCC 50509), revealed characteristic hypnospores of P. marinus upon Lugol's iodine staining. These comprehensive investigations underscore the conclusive confirmation of P. marinus in Korean waters and mark a significant milestone in our understanding of the distribution and characteristics of this parasite in previously unreported regions.

Gut microbiome diversity in a febrile seizure mouse model.

Purpose: Febrile seizures at a young age can provoke late-onset temporal lobe epilepsy. Since recent evidence has suggested that the gut microbiome affects central nervous system pathology across the blood-brain barrier, we hypothesized that febrile seizures alter the composition of the gut microbiome to provoke epilepsy. Methods: Third-generation C57BL/6 mice were separated into two groups (n = 5 each), and hot air was applied to only one group to cause febrile seizures. After two weeks of heat challenge, the fecal pellets acquired from each group were analyzed. Results: The gut microbiota of fecal pellets from each group revealed five taxa at the genus level and eight taxa at the species level that were significantly different in proportion between the groups. Conclusion: Although there was no significant difference in the overall diversity of the gut microbiota between the two groups, the identified heterogeneity may imply the pathognomonic causative relevance of febrile seizures and the development of epilepsy.

Comparative Effect of Glucose-Lowering Drugs for Type 2 Diabetes Mellitus on Stroke Prevention: A Systematic Review and Network Meta-Analysis.

BACKGRUOUND: There is still a lack of research on which diabetic drugs are more effective in preventing stroke. Our network metaanalysis aimed to compare cerebrovascular benefits among glucose-lowering treatments. METHODS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov registry for clinical trials from inception through May 25, 2021. We included both prespecified cerebrovascular outcomes and cerebrovascular events reported as severe adverse events. Subgroup analyses were conducted by stroke subtype, publication type, age of patients, baseline glycosylated hemoglobin (HbA1c), duration of type 2 diabetes mellitus, and cardiovascular risks. RESULTS: Of 2,861 reports and 1,779 trials screened, 79 randomized controlled trials comprising 206,387 patients fulfilled the inclusion criteria. In the pairwise meta-analysis, the use of glucagon-like peptide-1 (GLP-1) agonist was associated with a lower risk of total stroke compared with placebo (relative risk [RR], -0.17; 95% confidence interval [CI], -0.27 to -0.07). In the network meta- analysis, only the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitor was associated with a reduction of total stroke, compared with placebo (RR, 0.81; 95% CI, 0.67 to 0.98). In the subgroup analyses, the use of SGLT-2 inhibitor and GLP-1 agonist was associated with a lower risk of stroke in those with high HbA1c (≥8.0) and low-risk of cardiovascular disease, respectively. CONCLUSION: SGLT-2 inhibitors and GLP-1 agonists were shown to be beneficial for stroke prevention in patients with type 2 diabetes mellitus.

Topiramate dosage optimization for effective antiseizure management via population pharmacokinetic modeling.

OBJECTIVE: Despite the suggested topiramate serum level of 5-20 mg/L, numerous institutions have observed substantial drug response at lower levels. We aim to investigate the correlation between topiramate serum levels, drug responsiveness, and adverse events to establish a more accurate and tailored therapeutic range. METHODS: We retrospectively analyzed clinical data collected between January 2017 and January 2022 at Seoul National University Hospital. Drug responses to topiramate were categorized as "insufficient" or "sufficient" by reduction in seizure frequency ≥ 50%. A population pharmacokinetic model estimated serum levels from spot measurements. ROC curve analysis determined the optimal cutoff values. RESULTS: A total of 389 epilepsy patients were reviewed having a mean dose of 178.4 ± 117.9 mg/day and the serum level, 3.9 ± 2.8 mg/L. Only 5.6% samples exhibited insufficient response, with a mean serum level of 3.6 ± 2.5 mg/L while 94.4% demonstrated sufficient response, with a mean 4.0 ± 2.8 mg/L, having no statistical significance. Among the 69 reported adverse events, logistic regression analysis identified a significant association between ataxia and serum concentration (p = 0.04), with an optimal cutoff value of 6.5 mg/L. INTERPRETATION: This study proposed an optimal therapeutic concentration for topiramate based on patients' responsiveness to the drug and the incidence of adverse effects. We recommended serum levels below 6.5 mg/L to mitigate the risk of ataxia-related side effects while dose elevation was found unnecessary for suboptimal responders, as the drug's effectiveness plateaus at minimal doses.

Using spectral and temporal filters with EEG signal to predict the temporal lobe epilepsy outcome after antiseizure medication via machine learning.

Epilepsy is a neurological disorder in which the brain is transiently altered. Predicting outcomes in epilepsy is essential for providing feedback that can foster improved outcomes in the future. This study aimed to investigate whether applying spectral and temporal filters to resting-state electroencephalography (EEG) signals could improve the prediction of outcomes for patients taking antiseizure medication to treat temporal lobe epilepsy (TLE). We collected EEG data from a total of 46 patients (divided into a seizure-free group (SF, n = 22) and a non-seizure-free group (NSF, n = 24)) with TLE and retrospectively reviewed their clinical data. We segmented spectral and temporal ranges with various time-domain features (Hjorth parameters, statistical parameters, energy, zero-crossing rate, inter-channel correlation, inter-channel phase locking value and spectral information derived from Fourier transform, Stockwell transform, and wavelet transform) and compared their performance by applying an optimal frequency strategy, an optimal duration strategy, and a combination strategy. For all time-domain features, the optimal frequency and time combination strategy showed the highest performance in distinguishing SF patients from NSF patients (area under the curve (AUC) = 0.790 ± 0.159). Furthermore, optimal performance was achieved by utilizing a feature vector derived from statistical parameters within the 39- to 41-Hz frequency band with a window length of 210 s, as evidenced by an AUC of 0.748. By identifying the optimal parameters, we improved the performance of the prediction model. These parameters can serve as standard parameters for predicting outcomes based on resting-state EEG signals.

[Hemodynamic Changes in Chronic Liver Disease].

Chronic liver disease causes hemodynamic changes in the body depending on the degree of progression. These hemodynamic changes begin with splanchnic vasodilation, with complications beginning to appear as the hyperdynamic changes occur. As chronic liver disease progresses, increased splanchnic vasodilation and hyperdynamic changes worsen portal hypertension and help cause or worsen chronic liver disease complications, such as ascites. Ultimately, the effective plasma volume and blood pressure decrease in the terminal stage.

Electroconvulsive therapy and seizure: a double-edged sword?

Electroconvulsive therapy (ECT) is a widely used therapeutic option of drug-refractory psychiatric disorders. ECT treats psychiatric symptoms by inducing brief controlled seizures through electrical stimulation, but ECT does not generally cause prolonged seizures or epilepsy. However, several studies have reported cases of prolonged seizures after ECT. This review aimed to determine the mechanism of epileptogenesis with neurobiological changes after ECT. Contrary to epileptogenesis by ECT, several cases have reported that ECT was successfully applied for treatment of refractory status epilepticus. In addition, ECT might be applied to hyperkinetic movement and psychiatric symptoms of encephalitis. We also investigated the anticonvulsant mechanism of ECT and how it controls encephalitis symptoms.

Clonal Hematopoiesis and Acute Ischemic Stroke Outcomes.

OBJECTIVE: The effect of clonal hematopoiesis of indeterminate potential (CHIP) on the manifestation and clinical outcomes of acute ischemic stroke (AIS) has not been fully elucidated. METHODS: Patients with AIS were included from a prospective registry coupled with a DNA repository. Targeted next-generation sequencing on 25 genes that are frequently mutated in hematologic neoplasms was performed. The prevalence of CHIP was compared between patients with AIS and age-matched healthy individuals. A multivariate linear or logistic regression model was used to assess the association among CHIP and stroke severity, hemorrhagic transformation, and functional outcome at 90 days. RESULTS: In total, 380 patients with AIS (mean age = 67.2 ± 12.7 years; 41.3% women) and 446 age-matched controls (mean age = 67.2 ± 8.7 years; 31.4% women) were analyzed. The prevalence of CHIP was significantly higher in patients with AIS than in the healthy controls (29.0 vs 22.0%, with variant allele frequencies of 1.5%, p = 0.024). PPM1D was found to be most significantly associated with incident AIS (adjusted odds ratio [aOR] = 7.85, 95% confidence interval [CI] = 1.83-33.63, p = 0.006). The presence of CHIP was significantly associated with the initial National Institutes of Health Stroke Scale (NIHSS) score (ß = 1.67, p = 0.022). Furthermore, CHIP was independently associated with the occurrence of hemorrhagic transformation (65/110 clonal hematopoiesis positive [CH+] vs 56/270 CH negative [CH-], aOR = 5.63, 95% CI = 3.24-9.77, p < 0.001) and 90-day functional disability (72/110 [CH+] vs 99/270 [CH-], aOR = 2.15, 95% CI = 1.20-3.88, p = 0.011). INTERPRETATION: CH was significantly associated with incident AIS. Moreover, particularly, sequence variations in PPM1D, TET2, and DNMT3A represent a new prognostic factor for AIS. ANN NEUROL 2023;94:836-847.

Comparative effects of nebivolol and carvedilol on left ventricular diastolic function in older patients with heart failure and preserved ejection fraction.

Background: Although many studies have compared carvedilol and nebivolol in heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF), such comparative studies for the elderly have not been reported yet. Nebivolol is known to be effective for improving diastolic function of elderly patients with HF. Thus, this study aimed to determine whether nebivolol could improve LV diastolic function to a greater extent than carvedilol in older patients aged over 70 years. Methods: This trial was a prospective, randomized, open-label, single-center, active-controlled study that enrolled 62 patients with class II or III HF over 70 years of age with an LVEF ≥40%. Patients were randomized into a carvedilol group or a nebivolol group. Transthoracic echocardiography was performed at baseline and 12 months by the same investigator who was blinded to clinical data. The primary endpoint was E/e' measured by echocardiographic evaluation 12 months after treatment. Results: The median duration of follow-up was 24 months. Baseline clinical characteristics and echocardiographic parameters, such as LV diastolic function indices, did not differ significantly between carvedilol and nebivolol groups. Twelve-month follow-up echocardiography data showed no significant difference in E/e' or other LV diastolic function indices between the two groups. There were no significant changes in echocardiographic parameters over 12 months in either group. Conclusions: There was no difference between carvedilol and nebivolol for improving diastolic function of elderly HF patients with LVEF ≥40%. This study showed no superiority of nebivolol over carvedilol in elderly patients with HF.

Improving performance robustness of subject-based brain segmentation software.

Purpose: Artificial intelligence (AI)-based image analysis tools to quantify the brain have become commercialized. However, insufficient data for learning and scanner specificity is a limitation for achieving high quality. In the present study, the performance of personalized brain segmentation software when applied to multicenter data using an AI model trained on data from a single institution was improved. Methods: Preindicators of brain white matter (WM) information from the training dataset were utilized for preprocessing. During learning, data of cognitively normal (CN) individuals from a single center were utilized, and data of CN individuals and Alzheimer disease (AD) patients enrolled in multiple centers were considered the test set. Results: The preprocessing based on the preindicator (dice similarity coefficient [DSC], 0.8567) resulted in a better performance than without (DSC, 0.7921). The standard deviation (SD) of the WM region intensity (DSC, 0.8303) had a more substantial influence on the performance than the average intensity (DSC, 0.6591). When the SD of the test data WM intensity was smaller than the learning data, the performance improved (0.03 increase in lower SD, 0.05 decrease in higher SD). Furthermore, preindicator-based pretreatment increased the correlation of mean cortical thickness of the entire gray matter between Atroscan and FreeSurfer, and data augmentation without preprocessing did not.Both preindicator processing and data augmentation improved the correlation coefficient from 0.7584 to 0.8165. Conclusion: Data augmentation and preindicator-based preprocessing of training data can improve the performance of AI-based brain segmentation software, both increasing the generalizability and stability of brain segmentation software.

Five-Year Retention of Perampanel and Polytherapy Patterns: 328 Patients From a Single Center in South Korea.

BACKGROUND AND PURPOSE: Perampanel (PER) is an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid antagonist used to treat focal and generalized epilepsy. Comprehensive data from real-world settings with long-term follow-ups are still scarce. This study aimed to determine the factors related to PER retention and the polytherapy pattern with PER. METHODS: We reviewed all patients with epilepsy with a history of PER prescription during 2008-2017 and over a follow-up of >3 years. PER usage patterns and associated factors were analyzed. RESULTS: Among the 2,655 patients in the cohort, 328 (150 females, 178 males) were enrolled. The ages at onset and diagnosis were 21.1±14.7 years and 25.6±16.1 years (mean±standard deviation), respectively. The age at the first visit to our center was 31.8±13.8 years. Seizure types were focal, generalized, and unknown onset in 83.8%, 15.9%, and 0.3% of patients, respectively. The most common etiology was structural (n=109, 33.2%). The maintenance duration of PER was 22.6±19.2 months (range=1-66 months). The initial number of concomitant antiseizure medications was 2.4±1.4 (range=0-9). The most common regimen was PER plus levetiracetam (n=41, 12.5%). The median number of 1-year seizures before PER usage was 8 (range=0-1,400). A seizure reduction of >50% was recorded in 34.7% of patients (52.0% and 29.2% in generalized and focal seizures, respectively). The 1-, 2-, 3-, 4-, and 5-year retention rates for PER were 65.3%, 50.4%, 40.4%, 35.3%, and 21.5%, respectively. A multivariate analysis indicated that lower age at onset was associated with longer retention (p=0.01). CONCLUSIONS: PER was safely used in patients with diverse characteristics and was maintained for a long time in a real-world setting, especially in patients with a lower age at onset.

Lesion Detection Through MRI Postprocessing in Pathology-Proven Focal Cortical Dysplasia: Experience at a Single Institution in the Republic of Korea.

BACKGROUND AND PURPOSE: Focal cortical dysplasia (FCD) is one of the most common causes of drug-resistant epilepsy, and necessitates a multimodal evaluation to ensure optimal surgical treatment. This study aimed to determine the supportive value of the morphometric analysis program (MAP) in detecting FCD using data from a single institution in Korea. METHODS: To develop a standard reference for the MAP, normal-looking MRIs by two scanners that are frequently used in this center were chosen. Patients with drug-resistant epilepsy and FCD after surgery were candidates for the analysis. The three-dimensional T1-weighted MRI scans of the patients were analyzed as test cases using the MAP. RESULTS: The MRI scans of 87 patients were included in the analysis. The radiologist detected abnormal findings correlated with FCD (RAD positive [RAD(+)]) in 34 cases (39.1%), while the MAP could detect FCD in 25.3% of cases. A combination of the MAP (MAP[+] cases) with interpretations by the radiologist increased the detection to 42.5% (37 cases). The lesion detection rate was not different according to the type of reference scanners except in one case. MAP(+)/RAD(-) presented in three cases, all of which had FCD type IIa. The detection rate was slightly higher using the same kind of scanner as a reference, but not significantly (35.0% vs. 22.4% p=0.26). CONCLUSIONS: The results of postprocessing in the MAP for detecting FCD did not depend on the type of reference scanner, and the MAP was the strongest in detecting FCD IIa. We suggested that the MAP could be widely utilized without developing institutional standards and could become an effective tool for detecting FCD lesions.

Comparison of efficacy and safety between third-dose triple and third-dose dual antihypertensive combination therapies in patients with hypertension.

We compared the efficacy and safety of third-standard-dose triple and third-standard-dose dual antihypertensive combination therapies in patients with mild to moderate hypertension. This was a phase II multicenter, randomized, double-blind, parallel-group trial. After a 4-week placebo run-in period, 245 participants were randomized to the third-dose triple combination (ALC group; amlodipine 1.67 mg + losartan potassium 16.67 mg + chlorthalidone 4.17 mg) or third-dose dual combination (AL group; amlodipine 1.67 mg + losartan potassium 16.67 mg, LC group; losartan potassium 16.67 mg + chlorthalidone 4.17 mg, AC group; amlodipine 1.67 mg + chlorthalidone 4.17 mg) therapy groups and followed up for 8 weeks. The mean systolic blood pressure (BP) reduction was -18.3 ± 13.2, -13.0 ± 13.3, -16.3 ± 12.4, and -13.8 ± 13.2 mmHg in the ALC, AL, LC, and AC groups, respectively. The ALC group showed significant systolic BP reduction compared to the AL and AC groups at weeks 4 (P = .010 and P = .018, respectively) and 8 (P = .017 and P = .036, respectively). At week 4, the proportion of systolic BP responders was significantly higher in the ALC group (42.6%) than in the AL (22.0%), LC (23.3%), and AC (27.1%) groups (P = .013, P = .021, and P = .045, respectively). At week 8, the proportion of systolic and diastolic BP responders was significantly higher in the ALC group (59.7%) than in the AL (39.3%) and AC (42.4%) groups (P = .022 and P = .049, respectively) at week 8. Third-standard-dose triple antihypertensive combination therapy demonstrated early effective BP control compared to third-standard-dose dual combination therapies, without increasing adverse drug reactions in patients with mild-to-moderate hypertension.

Prasugrel-Based De-Escalation in Patients With Acute Coronary Syndrome According to Renal Function.

Background: Patients with coronary artery disease and impaired renal function are at higher risk for both bleeding and ischemic adverse events after percutaneous coronary intervention (PCI). Objectives: This study assessed the efficacy and safety of a prasugrel-based de-escalation strategy in patients with impaired renal function. Methods: We conducted a post hoc analysis of the HOST-REDUCE-POLYTECH-ACS study. Patients with available estimated glomerular filtration rate (eGFR) (n = 2,311) were categorized into 3 groups. (high eGFR: >90 mL/min; intermediate eGFR: 60 to 90 mL/min; and low eGFR: <60 mL/min). The end points were bleeding outcomes (Bleeding Academic Research Consortium type 2 or higher), ischemic outcomes (cardiovascular death, myocardial infarction, stent thrombosis, repeated revascularization, and ischemic stroke), and net adverse clinical event (including any clinical event) at 1-year follow-up. Results: Prasugrel de-escalation was beneficial regardless of baseline renal function (P for interaction = 0.508). The relative reduction in bleeding risk from prasugrel de-escalation was higher in the low eGFR group than in both the intermediate and high eGFR groups (relative reductions, respectively: 64% (HR: 0.36; 95% CI: 0.15-0.83) vs 50% (HR: 0.50; 95% CI: 0.28-0.90) and 52% (HR: 0.48; 95% CI: 0.21-1.13) (P for interaction = 0.646). Ischemic risk from prasgurel de-escalation was not significant in all eGFR groups (HR: 1.18 [95% CI: 0.47-2.98], HR: 0.95 [95% CI: 0.53-1.69], and HR: 0.61 [95% CI: 0.26-1.39]) (P for interaction = 0.119). Conclusions: In patients with acute coronary syndrome receiving PCI, prasugrel dose de-escalation was beneficial regardless of the baseline renal function.

Dynamic Alterations in Cerebral Hemodynamics Measured by Portable Near-Infrared Spectroscopy in Orthostatic Hypotension and Intolerance.

BACKGROUND: We aimed to evaluate dynamic alterations in cerebral total hemoglobin concentration (HbT) in individuals with orthostatic hypotension (OH) and orthostatic intolerance (OI) symptoms using a portable near-infrared spectroscopy (NIRS) system. METHODS: Participants comprised 238 individuals (mean age, 47.9 years) without a history of cardiovascular, neurodegenerative, or cerebrovascular diseases, including those with unexplained OI symptoms and healthy volunteers. Participants were categorized by the presence of OH based on the supine-to-stand blood pressure (BP) drop and OI symptoms using on OH questionnaires: classic OH (OH-BP), OH symptoms alone (OH-Sx), and control groups. Random case-control matching sets were constructed, resulting in 16 OH-BP and 69 OH-Sx-control sets. The time-derivative of HbT change in the prefrontal cortex during the squat-to-stand maneuver was measured using a portable NIRS system. RESULTS: There were no differences in demographics, baseline BP, and heart rate among matched sets. The peak time of maximum slope variation in HbT change, indicating the recovery rate and speed of cerebral blood volume (CBV) change, was significantly longer in OH-Sx and OH-BP groups than in the control group under transition to a standing position after squatting. In the OH-BP subgrouping, the peak time of maximum slope variation in HbT change was significantly longer only in OH-BP with OI symptoms, but did not differ between OH-BP without OI symptoms and controls. CONCLUSIONS: Our results suggest that OH and OI symptoms are associated with dynamic alterations in cerebral HbT. Regardless of the severity of the postural BP drop, OI symptoms are associated with prolonged CBV recovery.