Comparing Ictal Cardiac Autonomic Changes in Patients with Frontal Lobe Epilepsy and Temporal Lobe Epilepsy by Ultra-Short-Term Heart Rate Variability Analysis.

Background and Objectives: Abnormal epileptic discharges in the brain can affect the central brain regions that regulate autonomic activity and produce cardiac symptoms, either at onset or during propagation of a seizure. These autonomic alterations are related to cardiorespiratory disturbances, such as sudden unexpected death in epilepsy. This study aims to investigate the differences in cardiac autonomic function between patients with temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE) using ultra-short-term heart rate variability (HRV) analysis around seizures. Materials and Methods: We analyzed electrocardiogram (ECG) data recorded during 309 seizures in 58 patients with epilepsy. Twelve patients with FLE and 46 patients with TLE were included in this study. We extracted the HRV parameters from the ECG signal before, during and after the ictal interval with ultra-short-term HRV analysis. We statistically compared the HRV parameters using an independent t-test in each interval to compare the differences between groups, and repeated measures analysis of variance was used to test the group differences in longitudinal changes in the HRV parameters. We performed the Tukey-Kramer multiple comparisons procedure as the post hoc test. Results: Among the HRV parameters, the mean interval between heartbeats (RRi), normalized low-frequency band power (LF) and LF/HF ratio were statistically different between the interval and epilepsy types in the t-test. Repeated measures ANOVA showed that the mean RRi and RMSSD were significantly different by epilepsy type, and the normalized LF and LF/HF ratio significantly interacted with the epilepsy type and interval. Conclusions: During the pre-ictal interval, TLE patients showed an elevation in sympathetic activity, while the FLE patients showed an apparent increase and decrease in sympathetic activity when entering and ending the ictal period, respectively. The TLE patients showed a maintained elevation of sympathetic and vagal activity in the pos-ictal interval. These differences in autonomic cardiac characteristics between FLE and TLE might be relevant to the ictal symptoms which eventually result in SUDEP.

Stress cardiomyopathy associated with area postrema syndrome as a presentation of neuromyelitis optica: case report.

BACKGROUND: Stress cardiomyopathy (Takotsubo cardiomyopathy) is very rare in the central nervous system (CNS) demyelinating disorders. Although this dysfunction of the heart-brain axis has been reported in several case series related to multiple sclerosis (MS), stress cardiomyopathy by neuromyelitis optica (NMO), which is rarer CNS demyelinating disorder than MS, is extremely rare. Herein, we report a case of stress cardiomyopathy associated with a medullary lesion as a presentation of NMO. CASE PRESENTATION: A 30-year-old woman was treated by veno-arterial extracorporeal membrane oxygenation due to catastrophic cardiopulmonary dysfunction after prolonged and unexplained nausea, vomiting, and cough. Myoclonus on the limbs developed afterward. Taken with suspicion of area postrema syndrome (APS), the brain MRI showed a demyelinating lesion in the medulla oblongata. APS and severe heart failure by stress cardiomyopathy were completely resolved by ECMO and hydrocortisone therapy. However, the CNS demyelinating lesion recurred after 1 month. The patient was diagnosed with NMO evident by the presence of aquaporin-4 antibody; Steroid therapy improved her symptoms. CONCLUSION: NMO should be considered as one of the differential diagnoses in patients with APS preceding severe cardiopulmonary distress.

Sleep Disturbances and Phenoconversion in Patients with REM Sleep Behavior Disorder.

OBJECTIVE: We aimed to investigate relationships between sleep disturbances and phenoconversion to neurodegenerative diseases in patients with REM sleep behavior disorder (RBD). METHOD: Using a comprehensive sleep database in a university-affiliated hospital between December 2014 and March 2021, we reviewed the data of 226 patients with RBD (182 patients with idiopathic RBD (iRBD) and 44 patients with symptomatic RBD (sRBD) with a neurodegenerative disease). RESULTS: Among 226 patients with RBD (male, 61.5%), the mean age at RBD onset and mean disease duration were 59.4 ± 10.5 and 5.9 ± 5.6 years, respectively. Further, 111 (49.1%) patients had periodic limb movements during sleep (PLMS, PLM index ≥ 15/h), while 110 patients (48.7%) had comorbid obstructive sleep apnea (OSA, respiratory disturbance index ≥ 15/h). There was a positive correlation between age at RBD onset and the apnea-hypopnea index and Pittsburgh Sleep Quality Index. Compared to patients with iRBD, patients with sRBD showed a lower N3 sleep (3.3 ± 5.0 vs. 1.6 ± 3.1%, p = 0.004) and higher periodic limb movement index (36.3 ± 31.8 vs. 56.9 ± 47.5/h, p = 0.021) at the baseline. Among the 186 patients with iRBD, 18 (8.0%) developed neurodegenerative diseases (converters, mean follow-up duration: 2.5 ± 1.6 years) and 164 did not (non-converters, mean follow-up 2.4 ± 2.2 years). There was no significant between-group difference in the demographics and baseline clinical features. Continuous positive airway pressure (CPAP) therapy was prescribed in 101 patients with OSA; among them, 71 (70%) patients agreed to use it. CPAP improved dream enactment behaviors. CONCLUSION: In our study, 8.0% of patients with iRBD showed phenoconversion within a mean follow-up duration of 2.5 years. Polysomnographic parameters could not predict phenoconversion to neurodegenerative disease. However, approximately half of the patients with RBD presented with significant sleep disorders, including OSA or PLMS. CPAP therapy may alleviate RBD symptoms in patients with RBD-OSA.

Early Impairment of Chopsticks Skills in Parkinsonism Suggests Progressive Supranuclear Palsy.

BACKGROUND AND PURPOSE: Chopsticks are a primary eating utensil in East Asia, but systematic assessments of chopsticks skills in parkinsonian disorders is lacking. We aimed to identify any differences in chopsticks skills in the early stages of Parkinson's disease (PD) and atypical parkinsonism (AP), including progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal syndrome (CBS). METHODS: We consecutively recruited 111 patients with PD and 74 with AP (40 with PSP, 30 with MSA, and 4 with CBS) who were in a drug-naïve state. The motor and cognitive functions of the patients were evaluated using a standardized protocol. Everyday chopsticks skills were evaluated using a chopsticks questionnaire developed in-house. The chopsticks skills test (CST) involved counting the number of pills that the subject was able to carry using chopsticks between two dishes separated by 20 cm within 20 seconds. RESULTS: Patient responses to the questionnaire indicating poor chopsticks skills ("I cannot pick up some of the food items" or "I cannot use chopsticks anymore") were present in 23.0% of AP patients and 30% of PSP patients, compared to only 5.6% of PD patients [odd ratio (OR)=5.07 and OR=7.29, p≤0.001 in both]. The performance in the CST was worse in PSP than in PD (p<0.001). The CST results were correlated with hand motor skills including in the coinrotation test, timed figure-tapping test, and motor Unified Parkinson's Disease Rating Scale scores in all of the patient groups (p<0.001). In PSP, a decline in visuospatial function and frontal executive function was associated with a poor performance in the CST in addition to poor motor performance (p<0.05). CONCLUSIONS: Impairments in chopsticks skills were more common in PSP than in PD during the early stages of parkinsonism. This suggests that early functional impairment of chopsticks skills can be used as a warning sign for PSP.

Individual-Level Lesion-Network Mapping to Visualize the Effects of a Stroke Lesion on the Brain Network: Connectograms in Stroke Syndromes.

BACKGROUND AND PURPOSE: Similar-sized stroke lesions at similar locations can have different prognoses in clinical practice. Lesion-network mapping elucidates network-level effects of lesions that cause specific neurologic symptoms and signs, and also provides a group-level understanding. This study visualized the effects of stroke lesions on the functional brain networks of individual patients. METHODS: We enrolled patients with ischemic stroke who were hospitalized within 1 week of the stroke occurrence. Resting-state functional magnetic resonance imaging was performed 3 months after the index stroke. For image preprocessing, acute stroke lesions were visually delineated based on diffusion-weighted images obtained at admission, and the lesion mask was drawn using MRIcron software. Correlation matrices were calculated from 280 brain regions using the Brainnetome Atlas, and connectograms were visualized using in-house MATLAB code. RESULTS: We found characteristic differences in connectograms between pairs of patients who had comparable splenial, frontal cortical, cerebellar, and thalamocapsular lesions. Two representative patients with bilateral thalamic infarctions showed significant differences in their reconstructed connectograms. The cognitive function had recovered well at 3 months after stroke occurrence in patients with well-maintained interhemispheric and intrahemispheric connectivities. CONCLUSIONS: This pilot study has visualized the effects of stroke lesions on the functional brain networks of individual patients. Consideration of the neurobiologic mechanisms underlying the differences between their connectograms has yielded new hypotheses about differences in the effects of stroke lesions.

CXC motif ligand 12 as a novel diagnostic marker for papillary thyroid carcinoma.

BACKGROUND: We subjected chemokine (C-X-C motif) ligand 12 (CXCL12) to immunohistochemistry to determine its utility as a novel diagnostic marker for papillary thyroid carcinoma (PTC) in comparison to cytokeratin 19 (CK19), Hector Battifora mesothelial epitope-1 (HBME-1), and galectin-3. METHODS: We analyzed the expressions of CXCL12, CK19, HBME-1, and galectin-3 using immunohistochemical staining in 258 cases of thyroid lesions (196 PTCs and 62 thyroid lesions excluding PTC). RESULTS: Remarkably, CXCL12 expression was exclusively found in PTC compared to other thyroid lesions (90.8% vs 3.2%; p < .001). In total, 91.1% (62 of 68) of the variant PTCs and 90.6% of conventional type (116 of 128) were associated with CXCL12 immunohistochemical expression, irrespective of the histological subtype. In contrast, very few of the thyroid lesions, excluding PTC, were positive for CXCL12 (2 of 62; 3.2%). Diagnostic performances for PTCs were as follows: sensitivity, 90.8%; specificity, 96.8%; positive predictive value, 98.9%; negative predictive value, 76.9%; and diagnostic accuracy, 92.2%. CONCLUSION: Our findings indicate that CXCL12 might serve as an effective novel supplementary diagnostic marker for PTC.

Strong cytoplasmic expression of COX2 at the invasive fronts of gallbladder cancer is associated with a poor prognosis.

AIM: The significance of cell cycle proteins, p21 and p53, and cyclo-oxygenase-2 (COX2) is still controversial in gallbladder adenocarcinoma. Conflicting results exist with regard to the prognostic significance of p21 and p53 expression, and the strong association of gallbladder cancer with chronic inflammation makes it only natural that COX2 negativity is rarely encountered, even in non-neoplastic biliary epithelia. METHODS: The authors explored whether the p21 and p53-labelling indices (LI) and strong cytoplasmic COX2 expression differ in the central parts (TC) and invasive fronts (IF) of gallbladder cancer. Paraffin-embedded whole tissue sections of 67 gallbladder cancers were immunohistochemically analysed for p21, p53 and COX2-LI at the IF and TC, and results were correlated with the clinicopathological features. RESULTS: Significantly higher LI was seen in IF compared with TC for p21, p53 and COX2. COX2-LI-IF showed significant positive correlations with perineural and lymphatic invasion, higher T and N stages, and non-papillary gross morphology. Gall-bladder cancers with COX2-LI-IF≥30% showed decreased overall and disease-free survival, and COX2-LI-IF≥30% was an independent poor prognostic factor on multivariable analysis. Gall-bladder cancers with high COX2 and p21-LI-IF showed decreased overall and disease-free survival. CONCLUSIONS: The IF of gallbladder cancer is characterised by significantly increased expression of p21, p53 and strong COX2 expression, and strong cytoplasmic COX2 expression at IF is associated with a poorer prognosis. Heterogeneity between TC and IF should be considered in in situ molecular studies, especially during interpretation of immunohistochemical stain results and tissue microarray construction.