Neck rigidity: a pitfall for video head-impulse tests in Parkinson's disease.

Video head impulse tests (video-HITs) are commonly used for vestibular evaluation; however, the results can be contaminated by various artifacts, including technical errors, recording problems, and participant factors. Although video-HITs can be used in patients with Parkinson's disease (PD), the effect of neck rigidity has not been systematically investigated. This study aimed to investigate the effect of neck rigidity on video-HIT results in patients with PD. We prospectively recruited 140 consecutive patients with PD (mean age ± standard deviation = 68 ± 10 years, 69 men) between September 2021 and April 2024 at Korea University Medical Center. The video-HIT results were compared with those of 19 age- and sex-matched healthy participants. Neck rigidity was stratified as a subdomain of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale motor part (MDS-UPDRS-III). In 59 patients, the vestibulo-ocular reflex (VOR) gain was overestimated in at least one canal plane (58/140, 41%), mostly in the anterior canal (AC, n = 44), followed by the horizontal (HC, n = 15) and posterior canals (PC, n = 7). VOR gain overestimation was also observed in patients with no (18/58, 35%), subtle (20/58, 34%), or mild (17/58, 29%) neck rigidity. Multivariable logistic regression analysis showed that VOR overestimation was positively associated with neck rigidity (odds ratio [OR] [95% confidence interval] = 1.51 [1.01-2.25], p = 0.043). The head velocities of patients decreased during head impulses for the AC (p = 0.033 for the right AC; p = 0.014 for the left AC), whereas eye velocities were similar to those of healthy participants. Our findings suggest that neck rigidity may be a confounder that can contaminate video-HIT results. Thus, the results of video-HITs, especially for the AC, should be interpreted with the context of head velocity during head impulses in patients with neck rigidity.

Deterministic Orientation Control of Ferroelectric HfO2 Thin Film Growth by a Topotactic Phase Transition of an Oxide Electrode.

The scale-free ferroelectricity with superior Si compatibility of HfO2 has reawakened the feasibility of scaled-down nonvolatile devices and beyond the complementary metal-oxide-semiconductor (CMOS) architecture based on ferroelectric materials. However, despite the rapid development, fundamental understanding, and control of the metastable ferroelectric phase in terms of oxygen ion movement of HfO2 remain ambiguous. In this study, we have deterministically controlled the orientation of a single-crystalline ferroelectric phase HfO2 thin film via oxygen ion movement. We induced a topotactic phase transition of the metal electrode accompanied by the stabilization of the differently oriented ferroelectric phase HfO2 through the migration of oxygen ions between the oxygen-reactive metal electrode and the HfO2 layer. By stabilizing different polarization directions of HfO2 through oxygen ion migration, we can gain a profound understanding of the oxygen ion-relevant unclear phenomena of ferroelectric HfO2.

The semicircular canal function is preserved with little impact on falls in patients with mild Parkinson's disease.

INTRODUCTION: Postural instability is a cardinal symptom of Parkinson's disease (PD), which suggests the vestibular system may be affected in PD. This study aimed to determine whether vestibular dysfunction is associated with the risk of falls in PD. METHODS: We prospectively recruited patients with de-novo PD at a tertiary medical center between December 2019 and March 2023. During initial assessment, each patient was queried about falls within the preceding year. All patients underwent evaluation of video head-impulse tests (video-HITs), motion analysis, mini-mental state examination (MMSE), and Montreal Cognitive Assessment (MOCA). We determined whether head impulse gain of the vestibulo-ocular reflex (VOR) was associated with clinical severity of PD or risk of falls. RESULTS: Overall, 133 patients (mean age ± SD = 68 ± 10, 59 men) were recruited. The median Movement Disorder Society-Unified Parkinson's Disease Rating Scale motor part (MDS-UPDRS-III) was 23 (interquartile range = 16-31), and 81 patients (61 %) scored 2 or less on the Hoehn and Yahr scale. Fallers were older (p = 0.001), had longer disease duration (p = 0.001), slower gait velocity (p = 0.009), higher MDS-UPDRS-III (p < 0.001) and H&Y scale (p < 0.001), lower MMSE (p = 0.018) and MOCA scores (p = 0.001) than non-fallers. Multiple logistic regression showed that MDS-UPDRS-III had a positive association with falling (p = 0.004). Falling was not associated with VOR gain (p = 0.405). The VOR gain for each semicircular canal showed no correlation with the MDS-UPDRS-III or disease duration. CONCLUSIONS: The semicircular canal function, as determined by video-HITs, is relatively spared and has little effect on the risk of falls in patients with mild-to-moderate PD.

Scale for Ocular Motor Disorders in Ataxia (SODA) in Patients with Multiple System Atrophy.

A clinical scale fully dedicated to evaluating ocular motor abnormalities is required for now. We investigated the utility of a recently developed Scale for Ocular motor Disorders in Ataxia (SODA) in patients with multiple system atrophy (MSA). We prospectively assessed SODA in consecutive patients with MSA between August 2021 and August 2023 at the Korea University Medical Center. The results of the clinical exam-based SODA were compared with those measured using video-oculography (VOG-guided SODA). We also compared the findings with other established clinical scales targeting patients with MSA, including the Unified Multiple System Atrophy Rating Scale (UMSARS) I-II, Movement Disorder Society-Unified Parkinson's Disease Rating Scale motor part (UPDRS-III), Scale for Assessment of Rating of Ataxia (SARA), Composite Autonomic Symptom Score-31 (COMPASS-31), and Composite Autonomic Severity Score (CASS). Twenty patients were enrolled in our study (17 with cerebellar-type MSA and three with Parkinson-type MSA). Scores ranged from 1 to 14 (median [interquartile range (IQR)] = 8 [5-10]). Among the subscales, saccades had a median score of 2.5 (IQR = 1-3), followed by ocular pursuit (1 [0-1]), nystagmus (1 [0-2]), saccadic intrusions (1 [0-1]), vestibulo-ocular reflex (VOR) (0.5 [0-1]), ocular alignment (0 [0-1]), and VOR cancellation (1 [0-1]). The clinical-exam-based SODA (p = 0.020) and VOG-guided SODA (p = 0.034) positively correlated with disease duration. No correlation was found between clinical exam-based SODA and other scales. Skew deviation, gaze-evoked nystagmus, VOR cancellation, and smooth pursuit had the highest precision among the items. Ocular misalignment and spontaneous and positional nystagmus were frequently false positive and were poorly detected with clinical exam-based SODA. Six patients with repeated evaluation exhibited higher scores, along with deterioration documented on other clinical scales. The SODA can reliably predict neurodegeneration as an additional clinical surrogate in MSA.

Osmotic demyelination syndrome caused by rapid correction of hyperammonemia and continuous hyperbilirubinemia: a case report and review of the literature.

Osmotic demyelination syndrome (ODS) is an acute demyelinating disorder characterized by the loss of myelin in the center of the basis pons, defined as central pontine myelinolysis (CPM), and demyelination in locations outside the pons, defined as extrapontine myelinolysis (EPM). ODS including CPM and EPM is mainly caused by rapid correction of hyponatremia. However, there are several reports of ODS in medical conditions such as malnutrition; alcoholism; liver transplantation; malignancy; sepsis; and electrolyte imbalance including hypernatremia, hypokalemia, hypophosphatemia, and chronic illness. ODS caused by rapid correction of hyperammonemia or continuous hyperbilirubinemia without sodium fluctuations has rarely been reported. Because ODS may be irreversible, prevention is crucial. Herein, we report a case of ODS secondary to rapid correction of hyperammonemia and continuous hyperbilirubinemia.

Ocular Motor Findings Aid in Differentiation of Spinocerebellar Ataxia Type 17 from Huntington's Disease.

Differentiation of spinocerebellar ataxia type 17 (SCA17) from Huntington's disease (HD) is often challenging since they share the clinical features of chorea, parkinsonism, and dystonia. The ocular motor findings remain to be elucidated in SCA17, and may help differentiating SCA17 from HD. We retrospectively compared the ocular motor findings of 11 patients with SCA17 with those of 10 patients with HD. In SCA17, abnormal ocular motor findings included impaired smooth pursuit (9/11, 82%), dysmetric saccades (9/11, 82%), central positional nystagmus (CPN, 7/11, 64%), abnormal head-impulse tests (4/11, 36%), and horizontal gaze-evoked nystagmus (GEN, 3/11, 27%). Among these, CPN was more frequently observed in SCA17 than in HD (7/11 (64%) vs. 0/10 (0%), p = 0.004) while saccadic slowing was more frequently observed in HD than in SCA17 (8/10 (80%) vs. 2/11 (18%), p = 0.009). Of six patients with follow-up evaluation, five later developed bilateral saccadic hypermetria (n = 4), GEN (n = 1), CPN (n = 1), bilaterally abnormal smooth pursuit (n = 1), and hyperactive head-impulse responses (n = 1) along with a clinical decline. Ocular motor abnormalities can be utilized as a diagnostic marker for differentiation of SCA17 from HD as well as a surrogate marker for clinical decline in SCA17.

Regional Metabolic Changes Influencing Three-Dimensional Perception in Parkinson's Disease.

BACKGROUND AND PURPOSE: Stereopsis refers to the perception of depth and awareness of the distance of an object from the observer that results from the brain receiving visual stimuli from both eyes in combination. Patients with idiopathic Parkinson's disease (PD patients) typically experience problems with vision, eyeball movements, and visual perception due to degeneration of the cells that generate dopamine in the brain. We therefore hypothesized that stereopsis is affected more by visual cortical dysfunction in idiopathic PD than by retina and subcortical structural dysfunction. METHODS: We analyzed stereopsis in 12 PD patients and 7 healthy controls using a three-dimensional (3D) television (TV). Before allowing patients to watch TV, we examined their visual acuity and strabismus using the Titmus Stereo Fly Test, and evaluated their cognitive function using cognitive tests. The patients watched 3D and two-dimensional (2D) versions of a movie with an approximate duration of 17 minutes, and then completed a questionnaire about stereopsis. All subjects underwent brain F-18 fluorodeoxyglucose (FDG) positron-emission tomography after watching the 3D version of the movie. One week later, subjects watched the 2D version of the same movie under the same conditions. Each scan was analyzed using statistical parametric mapping (version 8) software. RESULTS: The visual cortex was activated less in the PD patients than in the healthy controls when watching the 2D or 3D movie. However, there was no significant difference between watching 2D and 3D movies in the PD patients or healthy controls. CONCLUSIONS: The lower activation of the primary visual cortex in PD patients suggests the presence of dysfunction of the visual cortex. In addition, there was less activation of the visual association cortex in PD patients when watching a 3D movie than in controls under the same conditions. This might be one reason why PD patients do not recognize real and dynamic stereopsis. These findings have clinical significance since they suggest that safety needs to be considered when making devices or programs using 3D or virtual reality for use by patients with various cerebral degenerative diseases.

Differentiating amnestic from non-amnestic mild cognitive impairment subtypes using graph theoretical measures of electroencephalography.

The purpose of this study was to explore different patterns of functional networks between amnestic mild cognitive impairment (aMCI) and non-aMCI (naMCI) using electroencephalography (EEG) graph theoretical analysis. The data of 197 drug-naïve individuals who complained cognitive impairment were reviewed. Resting-state EEG data was acquired. Graph analyses were performed and compared between aMCI and naMCI, as well as between early and late aMCI. Correlation analyses were conducted between the graph measures and neuropsychological test results. Machine learning algorithms were applied to determine whether the EEG graph measures could be used to distinguish aMCI from naMCI. Compared to naMCI, aMCI showed higher modularity in the beta band and lower radius in the gamma band. Modularity was negatively correlated with scores on the semantic fluency test, and the radius in the gamma band was positively correlated with visual memory, phonemic, and semantic fluency tests. The naïve Bayes algorithm classified aMCI and naMCI with 89% accuracy. Late aMCI showed inefficient and segregated network properties compared to early aMCI. Graph measures could differentiate aMCI from naMCI, suggesting that these measures might be considered as predictive markers for progression to Alzheimer's dementia in patients with MCI.

Head-impulse tests aid in differentiation of multiple system atrophy from Parkinson's disease.

The integrity of the vestibulo-ocular reflex (VOR) remains to be delineated in patients with parkinsonism. We aimed to define the findings of the VOR using head-impulse tests (HITs) and their differential diagnostic value in patients with Parkinson's disease (PD) and multiple system atrophy (MSA). From December 2019 to January 2021, 30 patients with PD and 23 patients with MSA (17 with cerebellar-type MSA and 6 with parkinsonian-type MSA) had a video-oculographic recording of HITs at two university hospitals in South Korea. Reversed (p = 0.034) and perverted (p = 0.015) catch-up saccades were more frequently observed in MSA than in PD during HITs. The gain difference between the ACs and the PCs were larger in MSA than in PD (p = 0.031), and positively correlated with the disease duration in patients with MSA (Spearman's coefficient = 0.512, p = 0.012). Multivariate logistic regression analysis showed that reversed (p = 0.044) and perverted (p = 0.039) catch-up saccades were more frequently associated with MSA than with PD during HITs. In conclusion, HITs aid in differentiation of MSA from PD, and may serve as a surrogate marker for the clinical decline.

Automated Classification of Normal Control and Early-Stage Dementia Based on Activities of Daily Living (ADL) Data Acquired from Smart Home Environment.

With the global trend toward an aging population, the increasing number of dementia patients and elderly living alone has emerged as a serious social issue in South Korea. The assessment of activities of daily living (ADL) is essential for diagnosing dementia. However, since the assessment is based on the ADL questionnaire, it relies on subjective judgment and lacks objectivity. Seven healthy seniors and six with early-stage dementia participated in the study to obtain ADL data. The derived ADL features were generated by smart home sensors. Statistical methods and machine learning techniques were employed to develop a model for auto-classifying the normal controls and early-stage dementia patients. The proposed approach verified the developed model as an objective ADL evaluation tool for the diagnosis of dementia. A random forest algorithm was used to compare a personalized model and a non-personalized model. The comparison result verified that the accuracy (91.20%) of the personalized model was higher than that (84.54%) of the non-personalized model. This indicates that the cognitive ability-based personalization showed encouraging performance in the classification of normal control and early-stage dementia and it is expected that the findings of this study will serve as important basic data for the objective diagnosis of dementia.

Growth modulation of atomic layer deposition of HfO2 by combinations of H2O and O3 reactants.

Atomic layer deposition (ALD) is a thin film deposition technique based on self-saturated reactions between a precursor and reactant vacuum conditions. A typical ALD reaction consists of the first half-reaction of the precursor and the second half-reaction of the counter reactant, in which the terminal groups on the surface change after each half-reaction. In this study, the effects of counter reactants on the surface termination and growth characteristics of ALD HfO2 thin films formed on Si substrates using tetrakis(dimethylamino)-hafnium (TDMAH) as a precursor were investigated. Two counter reactants, H2O and O3, were individually employed, as well as in combination with consecutive exposure by H2O-O3 and O3-H2O. The film growth behaviors and properties differed when the sequence of exposure of the substrate to the reactants was varied. Based on X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT) simulation, the changes are attributed to the effects of the surface terminations formed from different counter reactant combinations. The knowledge from this work could provide insight for precisely tuning the growth and properties of ALD films.

Did King Yeongjo (1694-1776) of Joseon Dynasty Korea suffer dementia during the last decade of his reign?

King Yeongjo, the 21st king of Joseon (18th Century Korea), reigned during the prime years of the dynasty and was its oldest king. Despite his many accomplishments, debate surrounds his reputed display of the symptoms of dementia during the last years of his life.  The King showed signs of dementia after 40 years of his regency in 1762 at the age of 69 years, including disorientation, cognitive impairment, amnestic disorder and so on. We examined evidence from the Annals of the Joseon Dynasty and related research papers. Additionally, dementia specialists were asked to undertake a survey to provide objectivity to the literary findings. Prior to his death in 1776, 25 meaningful dementia symptoms were recorded in the Annals across a 10-year period. However, despite indications of dementia, the Joseon dynasty supported him as a king and helped him retain his dignity until the end. This suggests that historical perception changes regarding dementia may also inform current-day attitudes to improve the living standards of patients suffering from dementia and related neuropsychiatric disorders.

Regional Gray Matter Volume Changes in Parkinson's Disease with Orthostatic Hypotension.

Neurodegenerative change in the central nervous system has been suggested as one of the pathophysiological mechanisms of autonomic nervous system dysfunction in Parkinson's disease (PD). We analyzed gray matter (GM) volume changes and clinical parameters in patients with PD to investigate any involvement in the brain structures responsible for autonomic control in patients with PD having orthostatic hypotension (OH). Voxel-based morphometry was applied to compare regional GM volumes between PD patients with and without OH. Multivariate logistic regression analysis using a hierarchical model was carried out to identify clinical factors independently contributing to the regional GM volume changes in PD patients with OH. The Sobel test was used to analyze mediation effects between the independent contributing factors to the GM volume changes. PD patients with OH had more severe autonomic dysfunction and reduction in volume in the right inferior temporal cortex than those without OH. The right inferior temporal volume was positively correlated with the Qualitative Scoring MMSE Pentagon Test (QSPT) score, reflecting visuospatial/visuoperceptual function, and negatively correlated with the Composite Autonomic Severity Score (CASS). The CASS and QSPT scores were found to be factors independently contributing to regional volume changes in the right inferior temporal cortex. The QSPT score was identified as a mediator in which regional GM volume predicts the CASS. Our findings suggest that a decrease in the visuospatial/visuoperceptual process may be involved in the presentation of autonomic nervous system dysfunction in PD patients.

Enhanced ferroelectric switching speed of Si-doped HfO2 thin film tailored by oxygen deficiency.

Investigations concerning oxygen deficiency will increase our understanding of those factors that govern the overall material properties. Various studies have examined the relationship between oxygen deficiency and the phase transformation from a nonpolar phase to a polar phase in HfO2 thin films. However, there are few reports on the effects of oxygen deficiencies on the switching dynamics of the ferroelectric phase itself. Herein, we report the oxygen- deficiency induced enhancement of ferroelectric switching properties of Si-doped HfO2 thin films. By controlling the annealing conditions, we controlled the oxygen deficiency concentration in the ferroelectric orthorhombic HfO2 phase. Rapid high-temperature (800 °C) annealing of the HfO2 film accelerated the characteristic switching speed compared to low-temperature (600 °C) annealing. Scanning transmission electron microscopy and electron energy-loss spectroscopy (EELS) revealed that thermal annealing increased oxygen deficiencies, and first-principles calculations demonstrated a reduction of the energy barrier of the polarization flip with increased oxygen deficiency. A Monte Carlo simulation for the variation in the energy barrier of the polarization flipping confirmed the increase of characteristic switching speed.

Facile Ferroelectric Phase Transition Driven by Si Doping in HfO2.

The recently discovered ferroelectricity in thin-film orthorhombic HfO2, which can be directly integrated into complementary metal-oxide semiconductor technology, has become an important research target. However, the use of orthorhombic HfO2 in practical devices has been limited by undesirable mixing with the monoclinic phase, which is nonpolar and thus degrades the ferroelectric properties. Here, we demonstrate that a Si dopant significantly stabilizes the ferroelectric phase because of its unique bonding characteristics, particularly its intrinsic tendency to form strong covalent bonds with O, thereby weakening the phase boundary to stabilize the ferroelectric orthorhombic phase over the nonpolar monoclinic phase, relatively. On the basis of our theoretical predictions, we conducted transmission electron microscopy measurements and confirmed that Si substitution doping indeed induced monoclinic structural components into the orthorhombic phase, which is a strong indication of the weakened phase boundary and subsequent facilitation of the ferroelectric transition. This work thus provides an atomic-scale picture for understanding the unique role of Si in promoting the ferroelectric phase and the dopant dependence on the wake-up effect in HfO2, offering a substantial advancement toward integrating ferroelectrics into practical devices.

Stable Subloop Behavior in Ferroelectric Si-Doped HfO2.

The recent demand for analogue devices for neuromorphic applications requires modulation of multiple nonvolatile states. Ferroelectricity with multiple polarization states enables neuromorphic applications with various architectures. However, deterministic control of ferroelectric polarization states with conventional ferroelectric materials has been met with accessibility issues. Here, we report unprecedented stable accessibility with robust stability of multiple polarization states in ferroelectric HfO2. Through the combination of conventional voltage measurements, hysteresis temperature dependence analysis, piezoelectric force microscopy, first-principles calculations, and Monte Carlo simulations, we suggest that the unprecedented stability of intermediate states in ferroelectric HfO2 is due to the small critical volume size for nucleation and the large activation energy for ferroelectric dipole flipping. This work demonstrates the potential of ferroelectric HfO2 for analogue device applications enabling neuromorphic computing.

Gabapentin versus Transdermal Fentanyl Matrix for the Alleviation of Chronic Neuropathic Pain of Radicular Origin: A Randomized Blind Multicentered Parallel-Group Noninferiority Trial.

A number of studies have been published proposing various approaches to the treatment of neuropathic pain; however, to our knowledge, no attempts have been made to compare gabapentin and fentanyl in patients with lumbar radiculopathy. We evaluated the relative efficacy and safety of fentanyl matrix and gabapentin for the treatment of chronic neuropathic pain of radicular origin. The study was designed as a randomized blind multicentered parallel-group noninferiority trial. A total of 108 patients with moderate-to-severe pain (≥4 intensity on an 11-point numeric rating scale) were randomly prescribed either fentanyl matrix or gabapentin over a period of 56 days. In the primary analysis, the noninferiority of fentanyl matrix treatment was evaluated in relation to the efficacy of gabapentin based on the pain intensity difference (PID) at 56 days after the first dose of the drugs. Secondary endpoints included pain relief, improvement in functional status (the Korean-Oswestry Disability Index (K-ODI)), improvement in depressive symptoms (Korean-Beck Depression Index (K-BDI)) between the 28th and 56th day, and adverse events (AEs). Analysis of the primary efficacy endpoint established the noninferiority of fentanyl matrix compared with gabapentin, with no statistically significant difference observed in the PID after 56 days for the two treatment groups. Similarly, analysis of pain relief revealed no significant differences between the groups on days 28 and 56. There was no difference in the K-ODI and K-BDI between the groups during the study period. The overall incidence of at least one AE was similar for fentanyl matrix (67.3%) and gabapentin (69.6%). The most commonly reported AEs for patients treated with fentanyl matrix and gabapentin included dizziness (30.8% vs. 44.6%, respectively), somnolence (26.9% vs. 35.7%), and constipation (15.4% vs. 17.9%). This study demonstrated that the analgesic effect of fentanyl matrix is noninferior in comparison with gabapentin and supports the use of fentanyl matrix as an effective and safe treatment for moderate-to-severe chronic neuropathic pain. This trial is registered with NCT01127100.