Association between physiotherapist sleep duration and working environment during the coronavirus disease 2019 pandemic in Japan: A secondary retrospective analysis study.

Studies have reported that health care professionals experienced a lack of sleep during the coronavirus disease 2019 (COVID-19) pandemic and that such lack of sleep and working environment affect their performance. However, to the authors' knowledge, no study has yet investigated the relationship between sleep duration and working environment among Japanese physiotherapists during the COVID-19 pandemic. This study retrospectively investigated the sleep duration of physiotherapists directly providing physiotherapy to patients with COVID-19 within the red zone and analyzed the association between sleep duration and working environment using logistic regression analysis. Among the 565 physiotherapists studied, the average sleep duration was 6 (6-7) h, and 381 (67.4%) had an average sleep duration of ≤6 h. Less experienced physiotherapists were 1.03 times more likely to sleep ≤6 h, and those in charge of patients with COVID-19 as the supervisor ordered were 0.64 times more likely to sleep ≤6 h. Moreover, physiotherapists with a significant increase in the frequency of internal online meetings and those who had been providing physiotherapy to patients with COVID-19 for >6 months were 2.34 and 2.05 times more likely to sleep ≤6 h, respectively. During the COVID-19 pandemic in Japan, two-thirds of the physiotherapists directly providing physiotherapy to patients with COVID-19 slept less than the recommended duration. This study highlights the need for appropriate workload and work hour management for physiotherapists according to their experience and workload, as well as establishing a medical care system that includes work rotation to ensure that the recommended sleep duration is satisfied.

Alterations in the hub structure of whole-brain functional networks in patients with drug-naïve schizophrenia: Insights from electroencephalography-based research.

Aim: This study aimed to identify atypical hubs in the whole-brain networks of patients with schizophrenia (SZ) and examine the effects of antipsychotic medications, using electroencephalography (EEG) data. Methods: We estimated the functional connectivity across all electrodes by applying the phase lag index to the EEG signals of 21 drug-naïve patients with SZ and 31 age-matched healthy controls. Betweenness centrality (BC), a measure of hub status, was calculated for each electrode and frequency band. Data from 14 patients were re-evaluated after initiating treatment with antipsychotic medications. Results: BC values decreased significantly at the Fz site in the beta band, decreased significantly at Pz in the gamma band, and increased significantly at O1 in the gamma band among patients with SZ. These changes persisted after antipsychotic treatment and were unrelated to clinical symptoms. Conclusion: The abnormal hub topology we observed, especially in the high-frequency band, may reflect the pathophysiology of SZ, and this study highlights the utility of BC analysis of EEG data for detecting alterations in the whole-brain networks of patients with SZ.

Home Based Exercise Rehabilitation Programs to Prevent Physical Frailty and Hospitalization-Associated Disability.

Daily health management and exercise are important for staying healthy and avoiding the need for long-term care. However, it is not easy to maintain regular exercise. Therefore, exercise needs to be done efficiently. In recent years, due to the aging population and increasing severity of illness, older patients often experience a significant decline in physical function, even with minimal rest, which often interferes with their daily life after discharge from the hospital. Frailty not only affects ADLs, but also strongly influences prognosis, including the development of atherosclerotic disease and rehospitalization. This perspective is a summary of the 51st Metropolitan Public Lecture held on June 17, 2023, and discusses exercise-based rehabilitation programs that can be delivered at home to prevent physical frailty and avoid hospitalization-related disability.

Relationship between prehabilitation responsiveness and postoperative physical functional recovery in cardiovascular surgery.

BACKGROUND: The purpose of this study was to examine the relationship between responsiveness to prehabilitation and postoperative recovery of physical function in cardiac surgery patients. METHODS: Ninety-three cardiac surgery patients (mean age: 76.4 years) were included in this retrospective cohort study. Preoperative physical function was measured using the Short Physical Performance Battery (SPPB), and a prehabilitation exercise program was implemented for the SPPB domains with low scores. Among the patients, those whose SPPB score was over 11 from the start of prehabilitation and remained over 11 on the day before surgery were defined as the high-functioning group, and those whose SPPB score improved by 2 points or more from the start of prehabilitation and exceeded 11 points were defined as the responder group. Those whose SPPB score did not exceed 11 immediately before surgery were classified as non-responders. The characteristics of each group and postoperative recovery of physical function were investigated. RESULTS: There were no serious adverse events during prehabilitation. Mean days of prehabilitation was 5.4 days. The responder group showed faster improvement in postoperative physical function and shorter time to ambulatory independence than the non-responder group. The non-responder group had lower preoperative skeletal muscle index, more severe preoperative New York Heart Association classification, and a history of musculoskeletal disease or stroke. CONCLUSION: There were responders and non-responders to prehabilitation among cardiac surgery patients. Cardiac surgery patients who respond to prehabilitation had faster recovery of physical function. Further research is needed to determine what type of prehabilitation is more effective in postoperative recovery of physical function in cardiac surgery patients.

Effect of Addition of Tannin Extract from Underutilized Resources on Allergenic Proteins, Color and Textural Properties of Egg White Gels.

Tannins, present in numerous plants, exhibit a binding affinity for proteins. In this study, we aimed to exploit this property to reduce the concentration of allergenic egg white proteins. Tannins were extracted, using hot water, from the lyophilized powder of underutilized resources, such as chestnut inner skin (CIS), young persimmon fruit (YPF), and bayberry leaves (BBLs). These extracts were then incorporated into an egg white solution (EWS) to generate an egg white gel (EWG). Allergen reduction efficacy was assessed using electrophoresis and ELISA. Our findings revealed a substantial reduction in allergenic proteins across all EWGs containing a 50% tannin extract. Notably, CIS and BBL exhibited exceptional efficacy in reducing low allergen levels. The addition of tannin extract resulted in an increase in the total polyphenol content of the EWG, with the order of effectiveness being CIS > YPF > BBL. Minimal color alteration was observed in the BBL-infused EWG compared to the other sources. Additionally, the introduction of tannin extract heightened the hardness stress, with BBL demonstrating the most significant effect, followed by CIS and YPF. In conclusion, incorporating tannin extract during EWG preparation was found to decrease the concentration of allergenic proteins while enhancing antioxidant properties and hardness stress, with BBL being particularly effective in preventing color changes in EWG.

Clinical and Pathological Features of FTDP-17 with MAPT p.K298_H299insQ Mutation.

BACKGROUND: MAPT is a causative gene in frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), a hereditary degenerative disease with various clinical manifestations, including progressive supranuclear palsy, corticobasal syndrome, Parkinson's disease, and frontotemporal dementia. OBJECTIVES: To analyze genetically, biochemically, and pathologically multiple members of two families who exhibited various phenotypes of the disease. METHODS: Genetic analysis included linkage analysis, homozygosity haplotyping, and exome sequencing. We conducted tau protein microtubule polymerization assay, heparin-induced tau aggregation, and western blotting with brain lysate from an autopsy case. We also evaluated abnormal tau aggregation by using anti-tau antibody and PM-PBB3. RESULTS: We identified a variant, c.896_897insACA, p.K298_H299insQ, in the MAPT gene of affected patients. Similar to previous reports, most patients presented with atypical parkinsonism. Biochemical analysis revealed that the mutant tau protein had a reduced ability to polymerize microtubules and formed abnormal fibrous aggregates. Pathological study revealed frontotemporal lobe atrophy, midbrain atrophy, depigmentation of the substantia nigra, and four-repeat tau-positive inclusions in the hippocampus, brainstem, and spinal cord neurons. The inclusion bodies also stained positively with PM-PBB3. CONCLUSIONS: This study confirmed that the insACA mutation caused FTDP-17. The affected patients showed symptoms resembling Parkinson's disease initially and symptoms of progressive supranuclear palsy later. Despite the initial clinical diagnosis of frontotemporal dementia in the autopsy case, the spread of lesions could explain the process of progressive supranuclear palsy. The study of more cases in the future will help clarify the common pathogenesis of MAPT mutations or specific pathogeneses of each mutation.

Validity Verification of Human Pose-Tracking Algorithms for Gait Analysis Capability.

Two-dimensional (2D) clinical gait analysis systems are more affordable and portable than contemporary three-dimensional (3D) clinical models. Using the Vicon 3D motion capture system as the standard, we evaluated the internal statistics of the Imasen and open-source OpenPose gait measurement systems, both designed for 2D input, to validate their output based on the similarity of results and the legitimacy of their inner statistical processes. We measured time factors, distance factors, and joint angles of the hip and knee joints in the sagittal plane while varying speeds and gaits during level walking in three in-person walking experiments under normal, maximum-speed, and tandem scenarios. The intraclass correlation coefficients of the 2D models were greater than 0.769 for all gait parameters compared with those of Vicon, except for some knee joint angles. The relative agreement was excellent for the time-distance gait parameter and moderate-to-excellent for each gait motion contraction range, except for hip joint angles. The time-distance gait parameter was high for Cronbach's alpha coefficients of 0.899-0.993 but low for 0.298-0.971. Correlation coefficients were greater than 0.571 for time-distance gait parameters but lower for joint angle parameters, particularly hip joint angles. Our study elucidates areas in which to improve 2D models for their widespread clinical application.

A Primal-Dual Box-Constrained QP Pressure Poisson Solver With Topology-Aware Geometry-Inspired Aggregation AMG.

We propose a new barrier-based box-constrained convex QP solver based on a primal-dual interior point method to efficiently solve large-scale pressure Poisson problems with non-negative pressure constraints, which commonly arise in liquid animation. The performance of prior active-set-based approaches is limited by the need to repeatedly update the active set. Our solver eliminates this issue by entirely avoiding the use of an active set, which in turn makes the inner problems of our Newton iteration process fully unconstrained. For efficiency, exploiting the solution uniqueness of convex QPs and the fact that the pressure constraints are simple box constraints, we aggressively update solution candidates without performing any step selection procedure (such as line search) and instead directly clamp candidates back to the bounds wherever constraint violations occur. Additionally, to accelerate the inner linear solves, we present a topology-aware geometry-inspired aggregation algebraic multigrid preconditioner and describe in detail several key performance optimizations that we incorporate. We demonstrate the efficacy of our solver in various practical scenarios and show that it often surpasses various alternatives in terms of speed and memory usage.

Reliability, stability during long-term storage, and intra-individual variation of circulating levels of osteopontin, osteoprotegerin, vascular endothelial growth factor-A, and interleukin-17A.

BACKGROUND: Studies in many populations have reported associations between circulating cytokine levels and various physiological or pathological conditions. However, the reliability of cytokine measurements in population studies, which measure cytokines in multiple assays over a prolonged period, has not been adequately examined; nor has stability during sample storage or intra-individual variation been assessed. METHODS: We assessed (1) analytical reliability in short- and long-term repeated measurements; (2) stability and analytical reliability during long-term sample storage, and (3) variability within individuals over seasons, of four cytokines-osteopontin (OPN), osteoprotegerin (OPG), vascular endothelial growth factor-A (VEGF-A), and interleukin-17A (IL-17A). Measurements in plasma or serum samples were made with commercial kits according to standard procedures. Estimation was performed by fitting a random or mixed effects linear model on the log scale. RESULTS: In repeated assays over a short period, OPN, OPG, and VEGF-A had acceptable reliability, with intra- and inter-assay coefficients of variation (CV) less than 0.11. Reliability of IL-17A was poor, with inter- and intra-assay CV 0.85 and 0.43, respectively. During long-term storage, OPG significantly decayed (- 33% per year; 95% confidence interval [- 54, - 3.7]), but not OPN or VEGF-A (- 0.3% or - 6.3% per year, respectively). Intra- and inter-assay CV over a long period were comparable to that in a short period except for a slight increase in inter-assay CV of VEGF-A. Within-individual variation was small for OPN and VEGF-A, with intra-class correlations (ICC) 0.68 and 0.83, respectively, but large for OPG (ICC 0.11). CONCLUSIONS: We conclude that OPN and VEGF-A can be reliably measured in a large population, that IL-17A is suitable only for small experiments, and that OPG should be assessed with caution due to degradation during storage and intra-individual variation. The overall results of our study illustrate the need for validation under relevant conditions when measuring circulating cytokines in population studies.

Incidence of Hospitalization-Associated Disability in Older Patients With Heart Failure.

BACKGROUND: This study determined the incidence of hospitalization-associated disability (HAD) and its characteristics in older patients with heart failure in Japan.Methods and Results: Ninety-six institutions participated in this nationwide multicenter registry study (J-Proof HF). From December 2020 to March 2022, consecutive heart failure patients aged ≥65 years who were prescribed physical rehabilitation during hospitalization were enrolled. Of the 9,403 patients enrolled (median age 83.0 years, 50.9% male), 3,488 (37.1%) had HAD. Compared with the non-HAD group, the HAD group was older and had higher rates of hypertension, chronic kidney disease, and cerebrovascular disease comorbidity. The HAD group also had a significantly lower Barthel Index score and a significantly higher Kihon checklist score before admission. Of the 9,403 patients, 2,158 (23.0%) had a preadmission Barthel Index score of <85 points. Binomial logistic analysis revealed that age and preadmission Kihon checklist score were associated with HAD in patients with a preadmission Barthel Index score of ≥85, compared with New York Heart Association functional classification and preadmission cognitive decline in those with a Barthel Index score <85. CONCLUSIONS: This nationwide registry survey found that 37.1% of older patients with HF had HAD and that these patients are indicated for convalescent rehabilitation. Further widespread implementation of rehabilitation for older patients with heart failure is expected in Japan.

The long-term effects of heated tobacco product exposure on the central nervous system in a mouse model of prodromal Alzheimer's disease.

Heated tobacco products (HTPs) have emerged as novel alternatives to conventional cigarettes (CCs), marketed by the tobacco industry as having a reduced potential for harm. Nevertheless, a significant dearth of information remains regarding the long-term effects of HTPs on the central nervous system (CNS). Here, we sought to shed light on the repercussions of prolonged exposure to HTPs on the CNS, employing a mouse model mimicking prodromal Alzheimer's disease (AD). Our study entailed subjecting App knock-in mice to 16 weeks of HTP exposure, administered 5 days per week, with serum cotinine concentration serving as confirmation of HTP exposure within this model. Histological analysis, aimed at assessing amyloid pathology, unveiled a minimal impact attributable to HTPs. However, exploration of differentially expressed genes in the cerebral cortex, using unadjusted p values, indicated an association between HTP exposure and non-inflammatory pathways, specifically linked to neurohypophyseal and neuropeptide hormone activity within the CNS. Of note, similar results have already been observed after exposure to CCs in vivo. Our study not only contributes insights into the potential non-inflammatory effects of HTPs within the context of AD pathogenesis but also underscores the significance of continued research to comprehend the full scope of their impact on the CNS.

Atypical instantaneous spatio-temporal patterns of neural dynamics in Alzheimer's disease.

Cognitive functions produced by large-scale neural integrations are the most representative 'emergence phenomena' in complex systems. A novel approach focusing on the instantaneous phase difference of brain oscillations across brain regions has succeeded in detecting moment-to-moment dynamic functional connectivity. However, it is restricted to pairwise observations of two brain regions, contrary to large-scale spatial neural integration in the whole-brain. In this study, we introduce a microstate analysis to capture whole-brain instantaneous phase distributions instead of pairwise differences. Upon applying this method to electroencephalography signals of Alzheimer's disease (AD), which is characterised by progressive cognitive decline, the AD-specific state transition among the four states defined as the leading phase location due to the loss of brain regional interactions could be promptly characterised. In conclusion, our synthetic analysis approach, focusing on the microstate and instantaneous phase, enables the capture of the instantaneous spatiotemporal neural dynamics of brain activity and characterises its pathological conditions.

Determination of Treatment Efficacy after Revascularization of Intermittent Claudication Patients by Physical Function Assessment.

PURPOSE: There have been few reports examining changes in physical activity (PA) after revascularization of lower extremities from the perspective of physical function at discharge. The purpose of this study was to clarify the effects of physical function before discharge on the amount of PA after discharge in patients who underwent revascularization. METHODS: The subjects were 34 Fontaine class II patients admitted for elective surgical revascularization or endovascular treatment at two hospitals from September 2017 to October 2019. Triaxial accelerometers were used to measure changes in sedentary behavior (SB) before admission and 1 month after discharge. Multiple regression analysis was performed on the 6-min walking distance (6MWD) at the time of discharge and the change in SB 1 month after discharge; the cutoff value was calculated from the receiver operating characteristic (ROC) curve. RESULTS: SB 1 month after discharge significantly decreased in the decreased SB group compared to the increased SB group (575.5 [400-745.2] vs. 649.5 [453.8-809.2], p <0.01). ROC curve was plotted with SB increase/decrease as the dependent variable and 6MWD at discharge as the independent variable; the cutoff value was 357.5 m. CONCLUSION: 6MWD measurement at discharge may help predict changes in SB after discharge.

Effect of in-patient cardiac rehabilitation at rehabilitation hospital for cardiology patients: two-center trial.

The effectiveness of cardiac rehabilitation (CR) in patients with cardiovascular disease requiring continuous CR from an acute care hospital to a convalescent rehabilitation hospital is unknown. Therefore, we compared the effect of CR in a rehabilitation hospital for patients with cardiovascular disease with that of those who underwent cardiovascular surgery. Sixty-nine consecutive patients were admitted to two rehabilitation hospitals for CR. Patients were classified by primary disease into two groups: patients with cardiovascular disease (cardiology group, 26 patients) and patients who underwent cardiovascular surgery (surgery group, 43 patients). Clinical information, physical function, cognitive function, activities of daily living (ADL), quality of life (QOL), amount of CR, and length of hospital stay were compared between the two groups. Compared with clinical features, age was significantly higher in the cardiology group (P < 0.001), and the preadmission Barthel index was significantly lower in the cardiology group (P = 0.025). Physical function at the time of transfer was significantly lower in the cardiology group than in the surgery group for the short physical performance battery (P < 0.001), gait speed (P = 0.005), and 6-min walking distance (P = 0.042). No significant difference was found in the amount of CR performed or the length of hospital stay, and no interaction effects were observed in improvements in physical function, exercise tolerance, or QOL. In conclusion, in rehabilitation hospitals, patients with cardiovascular disease were older, had lower preadmission ADL, and had lower a physical function at transfer than those who underwent cardiovascular surgery, but CR improved physical function and QOL to the same extent. The results suggest that the recovery of patients with cardiovascular disease may be similar to those who undergo cardiovascular surgery.

Corticobasal syndrome mimicking Foix-Chavany-Marie syndrome with suggested 4-repeat tauopathy by tau PET.

BACKGROUND: Corticobasal syndrome (CBS) is a neurodegenerative disease diagnosed based on clinical manifestations such as asymmetrical parkinsonism, limb apraxia, and speech and language impairment. The background pathology of CBS is commonly a variety of proteinopathies, but association with cerebrovascular disease has also been reported. Foix-Chavany-Marie syndrome (FCMS) is a rare neurological disorder characterized by facio-pharyngo-glossal diplegia with automatic-voluntary movement dissociation presenting with bilateral paresis of the facial, lingual, pharyngeal and masticatory muscles. FCMS is commonly attributable to stroke. Transactive response DNA binding protein of 43 kD (TDP-43) proteinopathy is also known as the pathological background of FCMS, while the pathological background of the majority of CBS cases consists of diverse tauopathies instead of TDP-43 proteinopathy. In this report, we describe a case mimicking FCMS that was finally diagnosed as CBS with suggested 4-repeat tauopathy. CASE PRESENTATION: A 68-year-old female started experiencing difficulty speaking followed by difficulty writing, and especially texting, several years before her visit. Her impairment had been gradually worsening, and she came to our hospital. On neurological examination, she demonstrated the facial apraxia, frontal lobe dysfunction, and upper motor neuron signs. She presented some characteristics suggestive of FCMS. Her symptoms exhibited rapid progression and myoclonus, parkinsonism, and left-side dominant cortical sensory deficit occurred, resulting in the fulfillment of diagnostic criteria for CBS after 9 months. Tau PET imaging displayed notable ligand uptake in the brainstem, subthalamic nuclei, basal ganglia, and bilateral subcortical frontal lobe, suggesting that her pathological background was 4-repeat tauopathy. As a result of her progressive dysphagia, she became unable to eat and passed away after 12 months. CONCLUSION: We hereby present an atypical case of CBS showing clinical features mimicking FCMS at first presentation. TDP-43 proteinopathy was suspected based on the clinical symptoms in the early stages of the disease; however, the clinical course and imaging findings including tau PET suggested that her pathological background was 4-repeat tauopathy.

Antibody-recognizing residues 188-211 of TMEM106B exhibit immunohistochemical reactivity with the TMEM106B C-terminal fragment.

Accumulation of TMEM106B fibrils composed of cleaved C-terminal fragments (CTF) of transmembrane protein 106B (TMEM106B) has recently been observed in the brains of elderly subjects and individuals with neurodegenerative diseases. To date, one antibody recognizing the residues 239-250 has been found to display immunoreactivity to the TMEM106B CTF, thereby defining TMEM106B C-terminal immunoreactive (TMEM-ir) material. Immunohistochemical characterization of the CTF using antibodies targeting different immunogens could further shed light on the attributes of TMEM-ir material and the biological relevance of TMEM106B fibril accumulation in vivo. Therefore, we generated and validated five polyclonal antibodies against distinct CTF immunogens, namely the residues 140-163, 164-187, 188-211, 239-250, and 253-274. The antibody recognizing the residues 239-250 (antibody no. 5: 239-250) was employed to identify cases positive for TMEM-ir material. Among the remaining four antibodies, antibody no. 3: 188-211 exhibited significant immunoreactivity in TMEM-ir material-positive cases. Comparative analyzes indicated that antibody no. 3: 188-211 and antibody no. 5: 239-250 likely recognized the same TMEM-ir material. The TMEM-ir material detected by antibody no. 3: 188-211 was observed across multiple brain cell types without co-localization with other pathogenic proteins. In conclusion, our findings suggest that the antibody recognizing the residues 188-211 displays immunohistochemical reactivity to TMEM-ir material. Therefore, in addition to the established antibody recognizing the residues 239-250, the antibody recognizing the residues 188-211 can potentially be used in immunohistochemical studies to further elucidate the significance of CTF accumulation in the brain.

Physical therapy in the intensive care unit: A cross-sectional study of three Asian countries.

BACKGROUND: Physical therapy (PT) is beneficial for critically ill patients, but the extent of its application in the intensive care unit (ICU) differs between countries. Here, we compared the extent of PT intervention in the ICU in Japan, the Philippines, and Taiwan by evaluating the sociodemographic and ICU-related profiles of ICU physical therapists. MATERIALS AND METHODS: In this cross-sectional study, a semistructured nationwide online survey was distributed to ICU physical therapists in the three countries. RESULTS: We analyzed the responses of 164 physical therapists from Japan, Philippines, and Taiwan. Significant differences were observed between the countries in all sociodemographic variables and the following ICU-related profiles of physical therapists: ICU work experience, duration of the ICU posting, number of hours per day spent in the ICU, on-call ICU PT service engagement, source of ICU patient referral, therapist-patient ratio, and ICU-related PT training participation (p < 0.05). Medical, surgical, and neurologic ICUs were the most common ICU workplaces of the ICU physical therapists, but only surgical and neurologic ICUs exhibited significant differences between the countries (p < 0.05). Standard PT techniques in the ICU were passive and active-assisted range of motion, positioning, and breathing exercises but were implemented with significantly different frequencies between the countries (p < 0.05). The most common challenge faced in ICU PT service delivery by respondents from all three countries was lack of training prior to ICU duty, and lack of training was even bigger challenge in Japan than in other two countries after adjustment of age, highest educational attainment, and work experience. CONCLUSION: The differences in the health-care system between Japan, the Philippines, and Taiwan were related to differences in the compliance with internationally recommended PT practice standards in the ICU, differences in the type of PT intervention prioritized, and the challenges encountered in ICU PT service delivery.

Chronic total occlusion of the left circumflex coronary artery with collateral channels from the bronchial artery: a case report.

Background: Chronic total occlusion (CTO) lesions contain various collateral channels. Only a few reports have described CTO with collateral channels from the bronchial arteries. Case summary: Herein, we report the case of a 59-year-old man with a left circumflex (LCX) coronary artery CTO with collateral channels from the bronchial arteries. The J-CTO score was 1. After confirming myocardial viability and myocardial ischaemia using a stress myocardial perfusion imaging test, we performed percutaneous coronary intervention for the CTO lesion. Successful revascularization was achieved by adopting the antegrade approach with the angiogram guidance of distal visualization using the bronchial artery. Discussion: Notably, there are no other reports of LCX CTO with collateral channels from the bronchial artery. Distal visualization of the distal true lumen is essential for the success of the antegrade approach. Furthermore, appropriate distal visualization helps to avoid unnecessary retrograde approaches and reduce complications.

[Case of hereditary Y69H (p.Y89H) transthyretin variant leptomeningeal amyloidosis presenting with drop attacks and recurrent transient language disorder].

We report a 73-year-old woman who started developing recurrent transient aphasia at the age of 66 years. During the attacks, she was aware she could not understand what was being said and both her spoken and written speech were meaningless. The attacks usually lasted for a few days, following which she could explain what had happened. Anti-epileptics did not improve her symptoms. She also noticed tremor of her right hand and gait disturbance at the age of 71 years. The recurrent transient aphasia was followed by drop attacks. At the time of her admission to our hospital, she showed paraplegia, phonological paraphasia, and difficulty in understanding complex sentences. Her language disturbance resembled a logopenic variant of primary progressive aphasia. However, the symptoms fluctuated for a few days and subsequently improved. Electroencephalography showed no abnormalities. Gadolinium-enhanced brain and spinal MRI showed diffuse leptomeningeal enhancement over the surface of the spinal cord, brain stem, and cerebrum on T1-weighed imaging. Surgical biopsy of a varicose vein in the subarachnoid space at the level of the Th11 spinal cord was performed. Pathological evaluation of the biopsied specimens revealed TTR-immunolabeled amyloid deposits in the subarachnoid vessel walls and on the arachnoid membrane. Gene analysis revealed c.265T>C, p.Y89H (Y69H) TTR mutation, which is known as one of the causative mutations of familial leptomeningeal amyloidosis. Leptomeningeal forms of transthyretin amyloidosis might present transient focal neurological episodes.