Upper common pathway analysis using late atrial premature depolarization in atrioventricular nodal reentry tachycardia.

BACKGROUND: Anatomic and electrophysiologic findings suggest that the actual circuit of atrioventricular nodal reentrant tachycardia (AVNRT) involves the perinodal atrium. However, occasional instances in which the atrium is dissociated from the AVNRT have led to the concept of an upper common pathway (UCP). OBJECTIVE: We aimed to assess the prevalence of UCP in AVNRT using a late atrial premature depolarization (LAPD) maneuver. METHODS: Patients who were diagnosed with typical AVNRT by electrophysiologic studies were enrolled. For evaluation of the presence of UCP, an LAPD was given at the coronary sinus ostium (osCS) during AVNRT, and then pacing was repeated incrementally every 10 ms. Electrograms in the earliest retrograde atrial activation site (ERAS) near the proximal His were mapped and recorded during the pacing. Results were interpreted as follows: absence of UCP-an LAPD from the osCS can reset the tachycardia without depolarizing the ERAS; presence of UCP-an LAPD from the osCS can depolarize the ERAS without resetting the tachycardia; and indeterminate-an LAPD from the osCS either resets the ERAS and tachycardia simultaneously or does not reset both. RESULTS: The LAPD maneuver was performed in 126 patients with AVNRT. It demonstrated an absence of UCP in 121 (96.0%) patients and the presence of UCP in 3 (2.4%) patients; the result was indeterminate in 2 (1.6%) patients. CONCLUSION: The LAPD maneuver revealed that the presence of UCP is indicated in only rare cases of AVNRT. In most AVNRT cases, the atrium is involved in the reentry circuit.

Feasibility and usefulness of cognitive monitoring using a new home-based cognitive test in mild cognitive impairment: a prospective single arm study.

BACKGROUND: The risk of dementia is increased in subjects with mild cognitive impairment (MCI). Despite the plethora of in-person cognitive tests, those that can be administered over the phone are lacking. We hypothesized that a home-based cognitive test (HCT) using phone calls would be feasible and useful in non-demented elderly. We aimed to assess feasibility and validity of a new HCT as an optional cognitive monitoring tool without visiting hospitals. METHODS: Our study was conducted in a prospective design during 24 weeks. We developed a new HCT consisting of 20 questions (score range 0-30). Participants with MCI (n = 38) were consecutively enrolled and underwent regular HCTs during 24 weeks. Associations between HCT scores and in-person cognitive scores and Alzheimer's disease (AD) biomarkers were evaluated. In addition, HCT scores in MCI participants were cross-sectionally compared with age-matched cognitively normal (n = 30) and mild AD dementia (n = 17) participants for discriminative ability of the HCT. RESULTS: HCT had good intra-class reliability (test-retest Cronbach's alpha 0.839). HCT scores were correlated with the Mini-Mental State Examination (MMSE), verbal memory delayed recall, and Stroop test scores but not associated with AD biomarkers. HCT scores significantly differed among cognitively normal, MCI, and mild dementia participants, indicating its discriminative ability. Finally, 32 MCI participants completed follow-up evaluations, and 8 progressed to dementia. Baseline HCT scores in dementia progressors were lower than those in non-progressors (p = 0.001). CONCLUSION: The feasibility and usefulness of the HCT were demonstrated in elderly subjects with MCI. HCT could be an alternative option to monitor cognitive decline in early stages without dementia.

An Analysis of the Determinants of the Health-Related Quality of Life in Asian Patients With Cluster Headaches During Cluster Periods Using the Time Trade-Off Method.

BACKGROUND AND PURPOSE: Patients with cluster headache (CH) exhibit impaired health-related quality of life (HRQoL). However, there have been few studies related to the HRQoL of patients with CH from Asian backgrounds. This study aimed to determine the impact of CH on HRQoL and to identify the factors affecting HRQoL in patients with CH during cluster periods. METHODS: This prospective study enrolled patients with CH from 17 headache clinics in South Korea between September 2016 and February 2021. The study aimed to determine HRQoL in patients with CH using the EuroQol 5 Dimensions (EQ-5D) index and the time trade-off (TTO) method. Age- and sex-matched headache-free participants were recruited as a control group. RESULTS: The study included 423 patients with CH who experienced a cluster period at the time. EQ-5D scores were lower in patients with CH (0.88±0.43, mean±standard deviation) than in the controls (0.99±0.33, p<0.001). The TTO method indicated that 58 (13.6%) patients with CH exhibited moderate-to-severe HRQoL deterioration. The HRQoL states in patients with CH were associated with current smoking patterns, headache severity, frequency, and duration, and scores on the Generalized Anxiety Disorder 7-item scale (GAD-7), Patient Health Questionnaire 9-item scale (PHQ-9), 6-item Headache Impact Test, and 12-item Allodynia Symptom Checklist. Multivariable logistic regression analyses demonstrated that the HRQoL states in patients with CH were negatively correlated with the daily frequency of headaches, cluster period duration, and GAD-7 and PHQ-9 scores. CONCLUSIONS: Patients with CH experienced a worse quality of life during cluster periods compared with the headache-free controls, but the degree of HRQoL deterioration varied among them. The daily frequency of headaches, cluster period duration, anxiety, and depression were factors associated with HRQoL deterioration severity in patients with CH.

Risk of epilepsy in gonadal teratoma: a nationwide population-based study.

Epilepsy is a common neurological disease. Systemic tumors are associated with an increased risk of epileptic events. Paraneoplastic encephalitis related to gonadal teratoma is frequently accompanied by seizures and life-threatening status epilepticus (SE). However, the risk of epilepsy in gonadal teratoma has not been studied. This study aims to investigate the relationship between epileptic events and gonadal teratoma. This retrospective cohort study used the Korean National Health Insurance (KNHI) database. The study population was divided into two study arms (ovarian teratoma vs. control and testicular teratoma vs. control) with 1:2 age and gender-matched control groups without a history of gonadal teratoma or other malignancy. Participants with other malignancies, neurologic disorders, and metastatic brain lesions were excluded. We observed the occurrence of epileptic events during the observation period (2013-2018) and investigated the risk of epileptic events in each gonadal teratoma group compared to controls. In addition, the influence of malignancy and tumor removal was investigated. The final analysis included 94,203 women with ovarian teratoma, 2314 men with testicular teratoma, and controls. Ovarian teratoma is associated with a higher risk of epilepsy without SE (HR, 1.244; 95% CI 1.112-1.391) and epilepsy with SE (HR, 2.012; 95% CI 1.220-3.318) compared to the control group. The risk of epilepsy without SE was higher in malignant ovarian teratoma (HR, 1.661; 95% CI 1.358-2.033) than in benign (HR, 1.172; 95% CI 1.037-1.324). Testicular teratoma did not show significant relations with epileptic events. The risk of epileptic events showed a tendency to decrease after removing the ovarian teratoma. This study found that ovarian teratoma is associated with a higher risk of epileptic events, especially in malignant tumors, whereas testicular teratoma did not show significant differences in epileptic events compared to the control group. This study adds to the current understanding of the association between gonadal teratoma and epileptic events.

Treatment pattern and response for cluster headache in Korea: A prospective multicenter observation study.

BACKGROUND: Only limited data are available regarding the treatment status and response to cluster headache in an Asian population. Therefore, this study aimed to provide a real-world treatment pattern of cluster headache and the response rate of each treatment in an Asian population. METHODS: Patients with cluster headache were recruited between September 2016 and January 2019 from 16 hospitals in Korea. At the baseline visit, we surveyed the patients about their previous experience of cluster headache treatment, and acute and/or preventive treatments were prescribed at the physician's discretion. Treatment response was prospectively evaluated using a structured case-report form at 2 ± 2 weeks after baseline visit and reassessed after three months. RESULTS: Among 295 recruited patients, 262 experiencing active bouts were included. Only one-third of patients reported a previous experience of evidence-based treatment. At the baseline visit, oral triptans (73.4%), verapamil (68.3%), and systemic steroids (55.6%) were the three most common treatments prescribed by the investigators. Most treatments were given as combination. For acute treatment, oral triptans and oxygen were effective in 90.1% and 86.8% of the patients, respectively; for preventive treatment, evidence-based treatments, i.e. monotherapy or different combinations of verapamil, lithium, systemic steroids, and suboccipital steroid injection, helped 75.0% to 91.8% of patients. CONCLUSION: Our data provide the first prospective analysis of treatment responses in an Asian population with cluster headache. The patients responded well to treatment despite the limited availability of treatment options, and this might be attributed at least in part by combination of medications. Most patients were previously undertreated, suggesting a need to raise awareness of cluster headache among primary physicians.

Development of a home-based cognitive test for cognitive monitoring in subjective cognitive decline with high risk of Alzheimer's disease.

BACKGROUND AND PURPOSE: Subjective cognitive decline (SCD) indicates a self-perceived persistent cognitive worsening despite of normal performance in standard neuropsychological tests. Owing to its heterogeneity and potential risk of Alzheimer's disease, baseline biomarkers to predict cognitive decline are important. In the present study, we developed a home-based cognitive test (HCT) to monitor cognitive changes regularly without visiting hospitals. This study aims to compare cognitive and biomarker trajectories during a 48-month period between amyloid positive SCD and amyloid negative SCD subjects. METHODS: Data will be collected from a prospective observational cohort study conducted in South Korea. Eighty participants with SCD aged ≥ 60 years are eligible for the study. All participants undergo annual neuropsychological tests and neurological examinations, bi-annual brain MRI scans and plasma amyloid markers, and baseline florbetaben Positron Emission Tomography scans. The amyloid burden and regional volumes will be measured. Cognitive and biomarker changes will be compared between the amyloid-positive SCD and amyloid negative SCD groups. Validation would be performed to assess reliability and feasibility of HCT. CONCLUSIONS: This study would suggest a perspective on SCD in terms of cognitive and biomarker trajectories. Baseline characteristics and biomarker status might affect faster cognitive decline and future biomarker trajectories. In addition, HCT could be an alternative option of in-person neuropsychological tests to track cognitive changes without visiting hospitals.

Efficacy and safety of oxiracetam in patients with vascular cognitive impairment: A multicenter, randomized, double-blinded, placebo-controlled, phase IV clinical trial.

BACKGROUND: Oxiracetam may have a modest effect on preventing cognitive decline. Exercise can also enhance cognitive function. This trial aims to investigate the effect of oxiracetam on post-stroke cognitive impairment and explore whether this effect is modified by exercise. Furthermore, the mechanisms that mediate this effect will be investigated through a neural network analysis. METHODS: This is a multicenter, randomized, double-blind, placebo-controlled phase IV trial. Patients who complained of cognitive decline 3 months after stroke and had a high risk of cognitive decline were eligible. Patients were randomly assigned to receive either 800 mg of oxiracetam or placebo twice daily for 36 weeks. After randomization, a predetermined exercise protocol was provided to each participant, and the degree of physical activity was assessed using wrist actigraphy at 4, 12, 24, and 36 weeks. Resting-state functional MRI was obtained in baseline and 36-week follow-up. Co-primary endpoints are changes in the Mini-Mental State Examination and Clinical Dementia Rating-Sum of Boxes. Secondary endpoints include changes in the NINDS-CSN VCIHS-Neuropsychology Protocol, Euro QoL, patient's global assessment, and functional network connectivity. If there is a significant difference in physical activity between the two groups, the interaction effect between physical activity and the treatment group will be examined. A total of 500 patients were enrolled from February 2018, and the last patient's final follow-up was completed in September 2022. CONCLUSION: This trial is meaningful not only to prove the efficacy of oxiracetam, but also evaluate whether exercise can modify the effects of medication and how cognitive function can be restored. Trial registrationhttp://cris.nih.go.kr (KCT0005137).

Untreated hypertension and prognosis paradox in acute ischemic stroke.

INTRODUCTION: This study is to explore the long-term functional outcome of antihypertensive medication-naïve, untreated hypertension (HTN) patients with acute ischemic stroke compared to those with no prior HTN and those with treated HTN. PATIENTS AND METHODS: We analyzed a prospectively collected stroke registry of all patients with acute ischemic stroke consecutively admitted to Incheon St. Mary's Hospital. Patients who received reperfusion therapy were excluded. Long-term functional outcomes were assessed at a 3-month follow-up visit using the modified Rankin Scale. RESULTS: A total of 1044 patients was enrolled. Compared to patients with no or treated HTN, those with untreated HTN had higher odds for more favorable outcomes (adjusted odds ratio (OR): 1.7 [95% CI: 1.0-2.7, p = 0.050*] and 1.7 [95% CI: 1.0-2.8, p = 0.047*], respectively) when the stroke was large vessel atherosclerosis (LAA)/cardioembolic (CE) with large vessel occlusion/stenosis. However, no such association was observed when there was no large vessel occlusion or stenosis, in total patients, or if the index stroke was related to SVO. In untreated HTN patients with LAA/CE and large vessel occlusion/stenosis compared to patients in the lowest mean arterial pressure quartile (< 96.7 mmHg), patients in the second and third highest quartiles had higher odds of favorable outcomes. CONCLUSIONS: Patients with untreated HTN had significantly more favorable outcomes at 3 months after ischemic stroke compared to those with no or treated HTN when the stroke was LAA/CE with large vessel occlusion/stenosis. Untreated HTN patients also showed an association between higher MAP and favorable outcomes.

The advantage of the mini-electrode-equipped catheter for the radiofrequency ablation of paroxysmal supraventricular tachycardia.

INTRODUCTION: Novel ablation catheters equipped with mini-electrodes (ME) offer high resolution mapping for target tissue. This study aimed to evaluate the mapping performance and efficacy of ME catheters in radiofrequency ablation (RFA) of paroxysmal supraventricular tachycardias (PSVTs). METHODS: We prospectively enrolled 136 patients undergoing RFA of PSVT including 76 patients with atrioventricular nodal reentrant tachycardia (AVNRT) and 60 patients with atrioventricular reentrant tachycardia (AVRT) or Wolff-Parkinson-White (WPW) syndrome. Patients were randomized to the ME group (ablation using ME catheters) or the control group (ablation using conventional catheters). The number of ablation attempt and cumulative ablation time to ablation endpoints, which was defined as an emergence of junctional rhythm in AVNRT or accessory pathway (AP) block in AVRT/WPW syndromes were compared. RESULTS: During ablation procedures, discrete slow pathway or AP electrograms were found in 27 (39.7%) patients in the ME group and 13 (19.1%) patients in the control group. The primary study outcomes were significantly lower in the ME group (ablation attempt number: 2.0 [1-4] vs. 3.0 [2-7] in the ME and control group, p = .032; ablation time: 23.5 [5.0-111.5] vs. 64.5 [16.0-185.0] s, p = .013). According to the PSVT diagnosis, ablation time to junctional rhythm was significantly shorter in the ME group in AVNRT. In AVRT/WPW syndrome, both ablation attempt number and ablation time to AP block were nonsignificantly lower in the ME group. CONCLUSION: The novel ME catheter was advantageous for identifying pathway potentials and reducing initial ablation attempt number and ablation time to reach acute ablation endpoint for PSVTs (ClinicalTrials.gov number, NCT04215640).

Diagnostic Delay and Its Predictors in Cluster Headache.

OBJECTIVE: Cluster headache (CH) is a rare, primary headache disorder, characterized of excruciating, strictly one-sided pain attacks and ipsilateral cranial autonomic symptoms. Given the debilitating nature of CH, delayed diagnosis can increase the disease burden. Thus, we aimed to investigate the diagnostic delay, its predictors, and clinical influence among patients with CH. METHODS: Data from a prospective multicenter CH registry over a 4-year period were analyzed. CH was diagnosed according to the International Classification of Headache Disorders (ICHD)-3 criteria, and diagnostic delay of CH was assessed as the time interval between the year of the first onset and the year of CH diagnosis. Patients were classified into three groups according to the tertiles of diagnostic delay (1st tertile, <1 year; 2nd tertile, 1-6 years; and 3rd tertile, ≥7 years). RESULTS: Overall, 445 patients were evaluated. The mean duration of diagnosis delay was 5.7 ± 6.7 years, (range, 0-36 years). Regarding the age of onset, majority of young patients (age <20 years) belonged to the third tertile (60%), whereas minority of old patients (>40 years) belonged to the third tertile (9.0%). For year of onset, the proportion of patients in the 3rd tertile was the highest for the groups before the publication year of the ICHD-2 (74.7%) and the lowest for the groups after the publication year of the ICHD-3 beta version (0.5%). Compared with the first CH, episodic CH [multivariable-adjusted odds ratio (aOR) = 5.91, 95% CI = 2.42-14.48], chronic CH (aOR = 8.87, 95% CI = 2.66-29.51), and probable CH (aOR = 4.12, 95% CI = 1.48-11.43) were associated with the tertiles of diagnostic delay. Age of onset (aOR = 0.97, 95% CI = 0.95-0.99) and PHQ-9 score (aOR = 0.96, 95% CI = 0.93-0.99) were inversely associated with the tertile of diagnostic delay. The prevalence of suicidal ideation was highest in the patients of the third tertile. The mean HIT-6 score increased significantly with the diagnostic delay (p = 0.041). CONCLUSIONS: Patients with a younger onset of CH have a higher risk of diagnostic delay. Nevertheless, the rate of delayed diagnosis gradually improved over time and with the publication of the ICHD criteria, supporting the clinical significance of diagnostic clinical criteria and headache education to reduce the disease burden of CH.

Characteristics of pre-cluster symptoms in cluster headache: A cross-sectional multicentre study.

BACKGROUND: Contrary to pre-attack symptoms before an individual cluster headache attack, little is known about the pre-cluster symptoms before the onset of cluster bouts. We previously described pre-attack symptoms before cluster headache attacks. The aim of this study was to investigate characteristics of pre-cluster symptoms in patients with episodic cluster headache. METHODS: In this multicentre study, 184 patients with episodic cluster headache were recruited between October 2018 and December 2020. They were interviewed by investigators and completed a structured questionnaire. To investigate pre-cluster and pre-attack symptoms, we assessed 20 symptoms and signs using the questionnaire. RESULTS: The upcoming cluster bout was predictable in 35.3% (n = 65/184) of the patients. When present, pre-cluster symptoms occurred at a median duration of 7 days (interquartile range, 2.3-14 days) before the onset of the cluster bout. Patients with pre-cluster symptoms showed a higher proportion of women, prevalence of pre-attack symptoms and seasonal rhythmicity, frequency of cluster headache attacks per day, and total number of cluster bouts compared to patients without pre-cluster symptoms. In univariable and multivariable logistic regression analyses, female sex was associated with the predictability of pre-cluster symptoms (odds ratio = 2.297, p = 0.016). CONCLUSIONS: The upcoming cluster bout was predicted in approximately 35% of patients with episodic cluster headache, which may allow for an earlier preventive treatment and help understand the pathophysiology.

The influence of endogenous and exogenous hormonal factors on migraine in spontaneous postmenopausal women: A nationwide population-based study in South Korea.

BACKGROUND: Hormonal and menstrual factors are known to influence migraines in women. However, studies in the postmenopausal period are relatively insufficient for clinical translation. This study investigated the influence of endogenous and exogenous hormonal factors on migraines in spontaneous menopausal women. METHODS: We obtained and analyzed the data related to hormonal factors from the Korean Health Examination database. A migraine diagnosis was identified using the Korean National Health Insurance Service database between 2009 and 2018. We observed migraine occurrence in spontaneous postmenopausal women. Study populations were divided into two groups depending on new diagnosis of migraine during the follow up periods. We investigated the association between endogenous and exogenous hormonal factors and migraine. RESULTS: 1,114,742 spontaneous postmenopausal women were enrolled. Migraine risk tended to increase in the shorter lifetime number of years of menstruation group compared to the group with lifetime number of years of menstruation ≥40 years. All of the hormone replacement therapy (HRT) groups showed higher risk compared with the non-HRT group. Migraine risk tends to increase with greater postmenopausal years compared to the postmenopausal <5 years group. CONCLUSION: Our study suggests that female hormonal factors, including endogenous and exogenous estrogen exposure, may be associated with migraine occurrence in spontaneous menopausal women.

The Influence of Amyloid Burden on Cognitive Decline over 2 years in Older Adults with Subjective Cognitive Decline: A Prospective Cohort Study.

BACKGROUND: Subjective cognitive decline (SCD) is a self-perceived cognitive worsening without objective cognitive impairment. Due to its heterogeneity and potential risk of Alzheimer's disease (AD), baseline biomarkers to predict progression are clinically important. In the present study, cognitive trajectories during a 24-month period were compared between amyloid-positive SCD (A+SCD) and amyloid-negative SCD (A-SCD) subjects, and biomarkers associated with memory decline were investigated. METHODS: Data from a prospective cohort study in Korea between 2016 and 2019 were analyzed. SCD subjects ≥50 years of age were eligible. All participants underwent neuropsychological tests, brain magnetic resonance imaging, and florbetaben positron emission tomography scans. Amyloid burden and regional volumes were measured. Cognitive changes corrected for age were compared between A+SCD and A-SCD groups. Biomarkers associated with memory decline were assessed. RESULTS: Forty-seven SCD subjects (69.9 ± 6.7 years, mini-mental state examination (MMSE) score 27.5) were enrolled, and 31 completed at least 1 annual follow-up (mean follow-up: 24.7 months). Baseline characteristics except age, hippocampal atrophy, and white matter hyperintensities were similar between A+SCDs (n = 12, 25.6%) and A-SCDs (n = 35). A+SCD subjects showed greater decline in the verbal memory function compared with the A-SCD subjects after adjustment for age. MMSE scores decreased more in the A+SCD (1.1 in the A+SCD; 0.55 in the A-SCD), although it was not statistically significant. Amyloid burden and baseline memory score were associated with memory decline. CONCLUSIONS: Within SCD, A+SCD subjects showed faster memory decline compared with the A-SCD subjects and amyloid burden might be associated with future memory decline in SCD.