Multiplexed Quantitative Proteomics Reveals Proteomic Alterations in Two Rodent Traumatic Brain Injury Models.

In many cases of traumatic brain injury (TBI), conspicuous abnormalities, such as scalp wounds and intracranial hemorrhages, abate over time. However, many unnoticeable symptoms, including cognitive, emotional, and behavioral dysfunction, often last from several weeks to years after trauma, even for mild injuries. Moreover, the cause of such persistence of symptoms has not been examined extensively. Recent studies have implicated the dysregulation of the molecular system in the injured brain, necessitating an in-depth analysis of the proteome and signaling pathways that mediate the consequences of TBI. Thus, in this study, the brain proteomes of two TBI models were examined by quantitative proteomics during the recovery period to determine the molecular mechanisms of TBI. Our results show that the proteomes in both TBI models undergo distinct changes. A bioinformatics analysis demonstrated robust activation and inhibition of signaling pathways and core proteins that mediate biological processes after brain injury. These findings can help determine the molecular mechanisms that underlie the persistent effects of TBI and identify novel targets for drug interventions.

Latent diffusion model-based MRI superresolution enhances mild cognitive impairment prognostication and Alzheimer's disease classification.

INTRODUCTION: Timely diagnosis and prognostication of Alzheimer's disease (AD) and mild cognitive impairment (MCI) are pivotal for effective intervention. Artificial intelligence (AI) in neuroradiology may aid in such appropriate diagnosis and prognostication. This study aimed to evaluate the potential of novel diffusion model-based AI for enhancing AD and MCI diagnosis through superresolution (SR) of brain magnetic resonance (MR) images. METHODS: 1.5T brain MR scans of patients with AD or MCI and healthy controls (NC) from Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) were superresolved to 3T using a novel diffusion model-based generative AI (d3T*) and a convolutional neural network-based model (c3T*). Comparisons of image quality to actual 1.5T and 3T MRI were conducted based on signal-to-noise ratio (SNR), naturalness image quality evaluator (NIQE), and Blind/Referenceless Image Spatial Quality Evaluator (BRISQUE). Voxel-based volumetric analysis was then conducted to study whether 3T* images offered more accurate volumetry than 1.5T images. Binary and multiclass classifications of AD, MCI, and NC were conducted to evaluate whether 3T* images offered superior AD classification performance compared to actual 1.5T MRI. Moreover, CNN-based classifiers were used to predict conversion of MCI to AD, to evaluate the prognostication performance of 3T* images. The classification performances were evaluated using accuracy, sensitivity, specificity, F1 score, Matthews correlation coefficient (MCC), and area under the receiver-operating curves (AUROC). RESULTS: Analysis of variance (ANOVA) detected significant differences in image quality among the 1.5T, c3T*, d3T*, and 3T groups across all metrics. Both c3T* and d3T* showed superior image quality compared to 1.5T MRI in NIQE and BRISQUE with statistical significance. While the hippocampal volumes measured in 3T* and 3T images were not significantly different, the hippocampal volume measured in 1.5T images showed significant difference. 3T*-based AD classifications showed superior performance across all performance metrics compared to 1.5T-based AD classification. Classification performance between d3T* and actual 3T was not significantly different. 3T* images offered superior accuracy in predicting the conversion of MCI to AD than 1.5T images did. CONCLUSIONS: The diffusion model-based MRI SR enhances the resolution of brain MR images, significantly improving diagnostic and prognostic accuracy for AD and MCI. Superresolved 3T* images closely matched actual 3T MRIs in quality and volumetric accuracy, and notably improved the prediction performance of conversion from MCI to AD.

Changes of neural coupling between cognitive and motor networks associated with dual-task performance in Parkinson's disease.

BACKGOUND: Although cognitive control is essential for efficient gait, the associations between cognitive and motor networks regarding gait in individuals with Parkinson's disease (PD) remain to be determined. Herein, we enrolled 28 PD and 28 controls to compare internetwork coupling among cognitive and motor networks and examine its relationship with single- and dual-task gait performance in PD. METHODS: The dorsal attention network (DAN), left and right frontoparietal control networks (FPNs), sensorimotor network, and lateral motor network were identified using resting-state functional magnetic resonance imaging data. The time taken to complete a 10-m walk test during cognitive or physical dual-tasks in PD was calculated representing gait performance. RESULTS: We observed that the internetwork couplings between the DAN and motor networks and between the motor networks decreased whereas those between the left FPN and DAN and motor networks increased in PD compared to controls using a permutation test. There was no significant correlation between the internetwork couplings and single- and dual-task gait performance in PD. Nevertheless, improved cognitive dual-task performance showed a positive correlation with the DAN and left FPN coupling and a negative correlation with the DAN and lateral motor network coupling in a good performance group. The opposite relationship was observed in the poor cognitive dual-task performance group. CONCLUSION: Our findings suggest a neural mechanism of cognitive control on gait to compensate for reduced goal-directed attention in PD who maintain cognitive dual-task performance.

Inter-rater and Intra-rater Reliability of the Videofluoroscopic Dysphagia Scale with the Standardized Protocol.

This study aimed to develop a standardized protocol for the assessment of videofluoroscopic dysphagia scale (VDS) and to demonstrate the inter-rater and intra-rater reliability of the VDS by applying the new standard protocol. A standardized protocol for the VDS was developed by dysphagia experts, including the original developer. To identify the reliability of the VDS using the protocol, 60 patients who underwent videofluoroscopic swallowing study (VFSS) for various etiologies were recruited retrospectively from three tertiary medical centers. Ten randomly selected cases were duplicated to evaluate the intra-rater reliability. Six physicians evaluated the VFSS data sets. Intraclass correlation coefficients were calculated for inter-rater and intra-rater reliability of the VDS score, and Gwet's kappa values for each VDS item were calculated. The inter-rater and intra-rater reliability of the total VDS score was 0.966 and 0.896, respectively. Notably, the evaluators' experience did not appear to have a significant impact on the reliability (physiatrists: 0.933/0.869, residents: 0.922/0.922). The reliability was consistent across different centers and dysphagia etiologies. The inter-rater and intra-rater reliability of the oral and pharyngeal sub-scores were 0.953/0.861 and 0.958/0.907, respectively. The inter-rater agreement of individual items ranged from 0.456 to 0.929, and nine items demonstrated good to very good level of agreement. Assessment of dysphagia using the VDS with the standard protocol showed excellent inter-rater and intra-rater reliabilities regardless of the evaluator's experience, VFSS equipment, and dysphagia etiologies. The VDS can be a useful assessment scale in the quantitative analysis of dysphagia based on VFSS findings.

Effects of Transcutaneous Auricular Vagus Nerve Stimulation on Cortical Excitability in Healthy Adults.

OBJECTIVE: Vagus nerve stimulation (VNS) has recently been reported to exert additional benefits for functional recovery in patients with brain injury. However, the mechanisms underlying these effects have not yet been elucidated. This study examined the effects of transcutaneous auricular VNS (taVNS) on cortical excitability in healthy adults. MATERIALS AND METHODS: We recorded subthreshold and suprathreshold single- and paired-pulse motor-evoked potentials (MEPs) in the right-hand muscles of 16 healthy adults by stimulating the left primary motor cortex. Interstimulus intervals were set at 2 milliseconds and 3 milliseconds for intracortical inhibition (ICI), and 10 milliseconds and 15 milliseconds for intracortical facilitation (ICF). taVNS was applied to the cymba conchae of both ears for 30 minutes. The intensity of taVNS was set to a maximum tolerable level of 1.95 mA. MEPs were measured before stimulation, 20 minutes after the beginning of the stimulation, and 10 minutes after the cessation of stimulation. RESULTS: The participants' age was 33.25 ± 7.08 years, and nine of 16 were male. No statistically significant changes were observed in the mean values of the single-pulse MEPs before, during, or after stimulation. Although the ICF showed an increasing trend after stimulation, the changes in ICI and ICF were not significant, primarily because of the substantial interindividual variability. CONCLUSIONS: The effect of taVNS on cortical excitability varied in healthy adults. An increase in ICF was observed after taVNS, although the difference was not statistically significant. Our findings contribute to the understanding of the mechanisms by which taVNS is effective in patients with brain disorders.

Deciphering Functional Connectivity Differences Between Motor Imagery and Execution of Target-Oriented Grasping.

This study aimed to delineate overlapping and distinctive functional connectivity in visual motor imagery, kinesthetic motor imagery, and motor execution of target-oriented grasping action of the right hand. Functional magnetic resonance imaging data were obtained from 18 right-handed healthy individuals during each condition. Seed-based connectivity and multi-voxel pattern analyses were employed after selecting seed regions with the left primary motor cortex and supplementary motor area. There was equivalent seed-based connectivity during the three conditions in the bilateral frontoparietal and temporal areas. When the seed region was the left primary motor cortex, increased connectivity was observed in the left cuneus and superior frontal area during visual and kinesthetic motor imageries, respectively, compared with that during motor execution. Multi-voxel pattern analyses revealed that each condition was differentiated by spatially distributed connectivity patterns of the left primary motor cortex within the right cerebellum VI, cerebellum crus II, and left lingual area. When the seed region was the left supplementary motor area, the connectivity patterns within the right putamen, thalamus, cerebellar areas IV-V, and left superior parietal lobule were significantly classified above chance level across the three conditions. The present findings improve our understanding of the spatial representation of functional connectivity and its specific patterns among motor imagery and motor execution. The strength and fine-grained connectivity patterns of the brain areas can discriminate between motor imagery and motor execution.

Development of Korea Neuroethics Guidelines.

BACKGROUND: Advances in neuroscience and neurotechnology provide great benefits to humans though unknown challenges may arise. We should address these challenges using new standards as well as existing ones. Novel standards should include ethical, legal, and social aspects which would be appropriate for advancing neuroscience and technology. Therefore, the Korea Neuroethics Guidelines were developed by stakeholders related to neuroscience and neurotechnology, including experts, policy makers, and the public in the Republic of Korea. METHOD: The guidelines were drafted by neuroethics experts, were disclosed at a public hearing, and were subsequently revised by opinions of various stakeholders. RESULTS: The guidelines are composed of twelve issues; humanity or human dignity, individual personality and identity, social justice, safety, sociocultural prejudice and public communication, misuse of technology, responsibility for the use of neuroscience and technology, specificity according to the purpose of using neurotechnology, autonomy, privacy and personal information, research, and enhancement. CONCLUSION: Although the guidelines may require a more detailed discussion after future advances in neuroscience and technology or changes in socio-cultural milieu, the development of the Korea Neuroethics Guidelines is a milestone for the scientific community and society in general for the ongoing development in neuroscience and neurotechnology.

Fully immersive virtual reality exergames with dual-task components for patients with Parkinson's disease: a feasibility study.

BACKGROUND: Dual-task training in Parkinson's disease (PD) improves spatiotemporal gait parameters, cognition, and quality of life. Virtual reality (VR) has been used as a therapeutic tool for patients to participate in activities in a safe environment, engage in multisensory experiences, and improve motivation and interest in rehabilitation. This study aimed to investigate the feasibility of fully immersive VR exergames with dual-task components in patients with PD. METHODS: We developed VR exergames (go/no-go punch game, go/no-go stepping game, and number punch game) to improve habitual behavior control using motor-cognitive dual-task performance in patients with PD. The participants underwent 10 sessions 2-3 times a week, consisting of 30 min per session. The Unified Parkinson's Disease Rating Scale, Timed Up and Go test (TUG) under single- and dual-task (cognitive and physical) conditions, Berg balance scale (BBS), Stroop test, trail-making test, and digit span were evaluated before and after intervention. The Simulator Sickness Questionnaire (SSQ) was used to assess VR cybersickness. Usability was assessed using a self-reported questionnaire. RESULTS: Twelve patients were enrolled and completed the entire training session. The mean age of participants was 73.83 ± 6.09 years; mean disease duration was 128.83 ± 76.96 months. The Hoehn and Yahr stages were 2.5 in seven patients and 3 in five patients. A significant improvement was observed in BBS and Stroop color-word test (p = 0.047 and p = 0.003, respectively). TUG time and dual-task interferences showed positive changes, but these changes were not statistically significant. The median SSQ total score was 28.05 (IQR: 29.92), 13.09 (IQR: 11.22), and 35.53 (IQR: 52.36) before, after the first session, and after the final session, respectively; the differences were not significant. Overall satisfaction with the intervention was 6.0 (IQR: 1.25) on a 7-point Likert-type scale. CONCLUSIONS: Fully immersive VR exergames combined with physical and cognitive tasks may be used for rehabilitation of patients with PD without causing serious adverse effects. Furthermore, the exergames using dual-task components improved executive function and balance. Further development of VR training content may be needed to improve motor and dual-task performances. Trial registration NCT04787549 ( https://clinicaltrials.gov/ct2/show/NCT04787549 ).

Fracture risk and impact of osteoporosis in patients with Parkinson's disease: a nationwide database study.

INTRODUCTION: Patients with Parkinson's disease (PD) showed an increased risk of fractures in previous studies and a high prevalence of osteoporosis is reportedly a potential contributor. We conducted a nationwide database study on the risk of fractures and the impact of osteoporosis on patients with PD compared to controls. MATERIALS AND METHODS: Using a nationwide database in South Korea, we identified incident patients with PD in 2004-2006 and selected four age- and sex-matched controls. We checked the occurrence rates of overall and hip fractures and plotted Kaplan-Meier curves and a Cox proportional hazards model to determine risk. We also conducted stratified analyses according to the presence or absence of osteoporosis. RESULTS: We identified 9126 patients with PD and 35,601 controls. Patients with PD had a greater probability of fractures throughout the study period in Kaplan-Meier curves, and an increased risk of overall (aHR 1.35, 95% CI 1.297-1.405) and hip (aHR 1.814, 95% CI 1.66-1.983) fractures in a Cox proportional hazards model. In the stratified analysis, the increased risk of overall fracture (aHR 1.333, 95% CI 1.273-1.396 and aHR 1.412, 95% CI 1.301-1.532, respectively) and hip fracture (aHR 1.773, 95% CI 1.604-1.96 and aHR 2.008, 95% CI 1.657-2.434, respectively) due to PD was similar between patients with and without osteoporosis. DISCUSSION: Patients with PD, with or without osteoporosis, are more likely to experience fractures, especially hip fractures. There seems to be no interaction between PD and osteoporosis in regard to the occurrence of fractures, and therefore no effect modification by osteoporosis.

The Association Between Antihypertensive Drug Use and Hospitalization for Pneumonia in the General Population: A Case-Crossover Study Using the National Health Insurance Database of Korea.

BACKGROUND: Previous studies have reported an association between pneumonia risk and the use of certain drugs. We investigated the relationship between antihypertensive drugs and pneumonia in the general population. METHODS: This case-crossover study utilized the nationwide data of South Korea. We included participants who were hospitalized for pneumonia. A single case period was defined as 30 days before pneumonia onset, and two control periods were established (90-120 and 150-180 days before pneumonia onset). Further, we performed sensitivity and subgroup analyses (according to the presence of diabetes, documented disability, and whether participants were aged ≥ 70 years). We used conditional logistic regression models adjusted for covariates, such as angiotensin-converting-enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), other antihypertensives, statins, antipsychotics, benzodiazepine, and the number of outpatient visits. RESULTS: In total, 15,463 subjects were included in this study. ACE inhibitors (adjusted odds ratio [aOR], 0.660; 95% confidence interval [CI], 0.558-0.781), ARBs (aOR, 0.702; 95% CI, 0.640-0.770), and other antihypertensive drugs (aOR, 0.737; 95% CI, 0.665-0.816) were significantly associated with reduced pneumonia risk. Subgroup analyses according to the presence of diabetes mellitus, documented disability, and whether participants were aged ≥ 70 years consistently showed the association of antihypertensives with a reduced risk of hospitalization for pneumonia. CONCLUSION: All antihypertensive drug types were related to a lower risk of hospitalization for pneumonia in the general population. Our results implied that frequent medical service usage and protective immunity were primarily related to a reduced risk of pneumonia in the general population of South Korea.

Association Between Antihypertensive Use and Hospitalized Pneumonia in Patients With Stroke: A Korean Nationwide Population-Based Cohort Study.

BACKGROUND: We aimed to examine the association between antihypertensive use and the incidence of hospitalized pneumonia in patients with a history of stroke. METHODS: In this case-crossover study, we obtained data from the Korean National Health Insurance Service-National Sample Cohort database. We included the data of patients with history of stroke who were admitted with a disease code of pneumonia. We analyzed the patients' exposure to antihypertensives in the 30 (single case period), 90-120, and 150-180 days (2 control periods) before the onset of pneumonia using conditional logistic regression analysis. Additionally, sensitivity analysis and subgroup analysis according to diabetes status, age, and documented disability were performed. RESULTS: Angiotensin II receptor blocker (ARB) use was associated with a reduced risk of hospitalized pneumonia (adjusted odds ratio [OR] [95% confidence interval; 95% CI]: 0.718 [0.576-0.894]). However, the use of angiotensin converting enzyme inhibitors and other antihypertensives were not associated with a change in hospitalized pneumonia incidence (adjusted OR [95% CI]: 0.902, [0.603-1.350] and 0.788 [0609-1.018], respectively). Subgroup analysis revealed that ARB use was associated with a reduced incidence of hospitalized pneumonia in patients with a history of stroke who were older than 65 years, but not in younger (≤ 65 years) group (adjusted OR [95% CI]: 0.687 [0.536-0.880]). CONCLUSION: ARB use is associated with a reduced incidence of hospitalized pneumonia in patients with a history of stroke, especially in older adults.

Clinical effectiveness of the sequential 4-channel NMES compared with that of the conventional 2-channel NMES for the treatment of dysphagia in a prospective double-blind randomized controlled study.

BACKGROUND: To date, conventional swallowing therapies and 2-channel neuromuscular electrical stimulation (NMES) are standard treatments for dysphagia. The precise mechanism of 2-channel NMES treatment has not been determined, and there are controversies regarding the efficacy of this therapy. The sequential 4-channel NMES was recently developed and its action is based on the normal contractile sequence of swallowing-related muscles. OBJECTIVE: To evaluate and compare the rehabilitative effectiveness of the sequential 4-channel NMES with that of conventional 2-channel NMES. METHODS: In this prospective randomized case-control study, 26 subjects with dysphagia were enrolled. All participants received 2- or 4-channel NMES for 2-3 weeks (minimal session: 7 times, treatment duration: 300-800 min). Twelve subjects in the 4-channel NMES group and eleven subjects in the 2-channel NMES group completed the intervention. Initial and follow-up evaluations were performed using the videofluoroscopic dysphagia scale (VDS), the penetration-aspiration scale (PAS), the MD Anderson dysphagia inventory (MDADI), the functional oral intake scale (FOIS), and the Likert scale. RESULTS: The sequential 4-channel NMES group experienced significant improvement in their VDS (oral, pharyngeal, and total), PAS, FOIS, and MDADI (emotional, functional, and physical subsets) scores, based on their pretreatment data. VDS (oral, pharyngeal, and total) and MDADI (emotional and physical subsets) scores, but not PAS and FOIS scores, significantly improved in the 2-channel NMES group posttreatment. When the two groups were directly compared, the 4-channel NMES group showed significant improvement in oral and total VDS scores. CONCLUSIONS: The sequential 4-channel NMES, through its activation of the suprahyoid and thyrohyoid muscles, and other infrahyoid muscles mimicking physiological activation, may be a new effective treatment for dysphagia. TRIAL REGISTRATION: clinicaltrial.gov, registration number: NCT03670498, registered 13 September 2018, https://clinicaltrials.gov/ct2/show/NCT03670498?term=NCT03670498&draw=2&rank=1 .

Development and Validation of 2D-LiDAR-Based Gait Analysis Instrument and Algorithm.

Acquiring gait parameters from usual walking is important to predict clinical outcomes including life expectancy, risk of fall, and neurocognitive performance in older people. We developed a novel gait analysis tool that is small, less-intrusive and is based on two-dimensional light detection and ranging (2D-LiDAR) technology. Using an object-tracking algorithm, we conducted a validation study of the spatiotemporal tracking of ankle locations of young, healthy participants (n = 4) by comparing our tool and a stereo camera with the motion capture system as a gold standard modality. We also assessed parameters including step length, step width, cadence, and gait speed. The 2D-LiDAR system showed a much better accuracy than that of a stereo camera system, where mean absolute errors were 46.2 ± 17.8 mm and 116.3 ± 69.6 mm, respectively. Gait parameters from the 2D-LiDAR system were in good agreement with those from the motion capture system (r = 0.955 for step length, r = 0.911 for cadence). Simultaneous tracking of multiple targets by the 2D-LiDAR system was also demonstrated. The novel system might be useful in space and resource constrained clinical practice for older adults.

Measurement and Correction of Stooped Posture during Gait Using Wearable Sensors in Patients with Parkinsonism: A Preliminary Study.

Stooped posture, which is usually aggravated during walking, is one of the typical postural deformities in patients with parkinsonism. However, the degree of stooped posture is difficult to quantitatively measure during walking. Furthermore, continuous feedback on posture is also difficult to provide. The purpose of this study is to measure the degree of stooped posture during gait and to investigate whether vibration feedback from sensor modules can improve a patient's posture. Parkinsonian patients with stooped posture were recruited for this study. Two wearable sensors with three-axis accelerometers were attached, one at the upper neck and the other just below the C7 spinous process of the patients. After being calibrated in the most upright posture, the sensors continuously recorded the sagittal angles at 20 Hz and averaged the data at every second during a 6 min walk test. In the control session, the patients walked with the sensors as usual. In the vibration session, sensory feedback was provided through vibrations from the neck sensor module when the sagittal angle exceeded a programmable threshold value. Data were collected and analyzed successfully in a total of 10 patients. The neck flexion and back flexion were slightly aggravated during gait, although the average change was <10° in most patients in both measurement sessions. Therefore, it was difficult to evaluate the effect of sensory feedback through vibration. However, some patients showed immediate response to the feedback and corrected their posture during gait. In conclusion, this preliminary study suggests that stooped posture could be quantitatively measured during gait by using wearable sensors in patients with parkinsonism. Sensory feedback through vibration from sensor modules may help in correcting posture during gait in selected patients.

Development of a Novel Prognostic Model to Predict 6-Month Swallowing Recovery After Ischemic Stroke.

Background and Purpose- The aim of this study was to explore clinical and radiological prognostic factors for long-term swallowing recovery in patients with poststroke dysphagia and to develop and validate a prognostic model using a machine learning algorithm. Methods- Consecutive patients (N=137) with acute ischemic stroke referred for swallowing examinations were retrospectively reviewed. Dysphagia was monitored in the 6 months poststroke period and then analyzed using the Kaplan-Meier method and Cox regression model for clinical and radiological factors. Bayesian network models were developed using potential prognostic factors to classify patients into those with good (no need for tube feeding or diet modification for 6 months) and poor (tube feeding or diet modification for 6 months) recovery of swallowing function. Results- Twenty-four (17.5%) patients showed persistent dysphagia for the first 6 months with a mean duration of 65.6 days. The time duration of poststroke dysphagia significantly differed by tube feeding status, clinical dysphagia scale, sex, severe white matter hyperintensities, and bilateral lesions at the corona radiata, basal ganglia, or internal capsule (CR/BG/IC). Among these factors, tube feeding status (P<0.001), bilateral lesions at CR/BG/IC (P=0.001), and clinical dysphagia scale (P=0.042) were significant prognostic factors in a multivariate analysis using Cox regression models. The tree-augmented network classifier, based on 10 factors (sex, lesions at CR, BG/IC, and insula, laterality, anterolateral territory of the brain stem, bilateral lesions at CR/BG/IC, severe white matter hyperintensities, clinical dysphagia scale, and tube feeding status), performed better than other benchmarking classifiers developed in this study. Conclusions- Initial dysphagia severity and bilateral lesions at CR/BG/IC are revealed to be significant prognostic factors for 6-month swallowing recovery. The prediction of 6-month swallowing recovery was feasible based on clinical and radiological factors using the Bayesian network model. We emphasize the importance of bilateral subcortical lesions as prognostic factors that can be utilized to develop prediction models for long-term swallowing recovery.

FHL1-mutated reducing body myopathy.

Here, we report about reducing body myopathy, associated with a mutation in the four and a half LIM domain 1 gene (FHL1), identified in a 40-year-old woman who was suffering from subtle muscle weakness since the age of six and a limping gait since the age of 22 years. In addition to her elevated muscle enzyme level and magnetic resonance imaging, myopathy was highly suspected considering progression of symptoms. Nerve conduction studies and electromyogram suggested myopathy. The muscle biopsy revealed severe dystrophic features with many reducing bodies on hematoxylin and eosin, nicotinomide adenine dinucleotide dehydrogenase-tetrazolium reductase (NADH-TR), and modified Gomori stains and ubiquitin immunohistochemistry. Whole-exome sequencing revealed Xq26.3 encoding FHL1 missense mutations (NM_001159704) in exon 4: p.C150R, c.T448C. FHL1-mutated "reducing body myopathy" is worth reporting based on its rarity and unique clinicopathologic features including ultrastructure. The confirmative diagnosis is still very difficult before gene analysis because clinical and pathological features of this disease overlap with other myofibrillar myopathies. We stress the importance of genotype-phenotype correlation to obtain a precise diagnosis.

Radiation Dose During Videofluoroscopic Swallowing Studies and Associated Factors in Pediatric Patients.

Although children are more radio-sensitive than adults, few studies have evaluated radiation dosage during videofluoroscopic swallowing study (VFSS) in children. The aim of the study was to investigate the radiation dosage using dose-area product (DAP) for VFSS in pediatric cases and to identify factors affecting the radiation dose. Patients aged 0-17 years who had undergone VFSS were included. The following data were collected retrospectively: DAP; fluoroscopic time; number of tried diets; and clinical characteristics including sex, age, etiology of dysphagia, and recommended feeding type. In the videofluoroscopic field, use of collimation and appearance of metal object, such as a lead apron or a wheel chair, was checked. A total of 290 VFSSs were included. The mean DAP was 5.78 ± 4.34 Gy cm2 with a mean screening time of 2.69 ± 1.30 min. The factors associated with the DAP included screening time, appearance of metal objects in the field, and use of collimation. In 98 cases with no metal object in the field and with collimation, the mean DAP was decreased to 2.96 ± 2.53 Gy cm2. This study evaluated the radiation dosage during VFSS in children according to age groups and the influencing factors such as screening time, appearance of metal objects in the field, and use of collimation in VFSS. To reduce radiation risk, it is important to identify and control modifiable factors.

Progression of Oropharyngeal Dysphagia in Patients with Multiple System Atrophy.

We investigated the progression of oropharyngeal dysphagia in patients with multiple system atrophy (MSA), with particular emphasis on MSA subtype variation. Fifty-nine MSA patients (31 MSA-P, 21 MSA-C, and 7 MSA-PC) who had undergone at least one videofluoroscopic swallowing study (VFSS) to evaluate dysphagia symptoms were included. Clinical data and VFSS findings were retrospectively evaluated using the videofluoroscopic dysphagia scale (VDS), and the results of each MSA subtype group were compared. The median latency to onset of diet modification from onset of MSA symptoms was 5.995 (95% CI 4.890-7.099) years in all MSA patients, 5.036 (95% CI 3.605-6.467) years in MSA-P, and 6.800 (95% CI 6.078-7.522) years in MSA-C (P = 0.035). The latency to onset of diet modification from onset of dysphagia symptoms was 2.715 (95% CI 2.132-3.298) years in all MSA patients, 2.299 (95% CI 1.194-3.403) years in MSA-P, and 5.074 (95% CI 2.565-7.583) years in MSA-C (P = 0.039). The latencies to onset of tube feeding from onset of MSA symptoms and dysphagia symptoms were 7.003 (95% CI 6.738-7.268) years and 3.515 (95% CI 2.123-4.907) years, respectively, in all MSA patients, without significant difference between subtypes. In the patients who underwent VFSS follow-up for ≥ 1 year, 6 oral VDS items significantly worsened; only two pharyngeal items exhibited significant changes. Patients with MSA-P commenced diet modification earlier than patients with MSA-C, despite no significant difference in the latency to onset of tube feeding. Deterioration of dysphagia may be more pronounced in the oral function of MSA patients.

Neuroprotective Effect of Chronic Intracranial Toxoplasma gondii Infection in a Mouse Cerebral Ischemia Model.

Toxoplasma gondii is an obligate intracellular protozoan parasite that can invade various organs in the host body, including the central nervous system. Chronic intracranial T. gondii is known to be associated with neuroprotection against neurodegenerative diseases through interaction with host brain cells in various ways. The present study investigated the neuroprotective effects of chronic T. gondii infection in mice with cerebral ischemia experimentally produced by middle cerebral artery occlusion (MCAO) surgery. The neurobehavioral effects of cerebral ischemia were assessed by measurement of Garcia score and Rotarod behavior tests. The volume of brain ischemia was measured by triphenyltetrazolium chloride staining. The expression levels of related genes and proteins were determined. After cerebral ischemia, corrected infarction volume was significantly reduced in T. gondii infected mice, and their neurobehavioral function was significantly better than that of the uninfection control group. Chronic T. gondii infection induced the expression of hypoxia-inducible factor 1-alpha (HIF-1α) in the brain before MCAO. T. gondii infection also increased the expression of vascular endothelial growth factor after the cerebral ischemia. It is suggested that chronic intracerebral infection of T. gondii may be a potential preconditioning strategy to reduce neural deficits associated with cerebral ischemia and induce brain ischemic tolerance through the regulation of HIF-1α expression.

Quantitative dynamic contrast-enhanced MR imaging shows widespread blood-brain barrier disruption in mild traumatic brain injury patients with post-concussion syndrome.

OBJECTIVES: To explore the utility of dynamic contrast-enhanced (DCE) MR imaging for quantitative analysis of blood-brain barrier disruption in mild traumatic brain injury (mTBI) patients with post-concussion syndrome (PCS). METHODS: Forty-four consecutive patients with PCS after mTBI and 32 controls were included in this retrospective study. Ktrans and ve from DCE MR imaging were analyzed at contrast-enhancing lesions, T2 hyperintense white matter (WM) lesions, normal-appearing white matter (NAWM), and predilection sites for diffuse axonal injury (LocationDAI). The Mann-Whitney U-test was performed to compare the parameters between mTBI patients and controls and the parameters were correlated with neuropsychological tests using Mann-Whitney U-test and Spearman rank correlation. RESULTS: The median ve of the T2 hyperintense WM lesions in mTBI patients (n=21) was higher than that of NAWM in controls (p=.027). Both median Ktrans and ve at NAWM were also significantly higher in mTBI patients than in controls (p=.023 and p=.029, respectively). In addition, mTBI patients had higher Ktrans and ve at LocationDAI than controls (p=.008 and p=.015, respectively). VLT (delayed recall) scores were significantly correlated with ve values at T2 hyperintense WM lesions (p=-0.767, p=.044). The median ve at LocationDAI was significantly higher in patients with atypical performance in the digit span test (forward) than in those with average or good performance (p=.043). CONCLUSIONS: mTBI patients with PCS had higher Ktrans and ve values than controls not only at T2 hyperintense WM lesions but also at NAWM and LocationDAI. BBB disruption may be implicated in development of PCS in mTBI patients. KEY POINTS: • mTBI patients with PCS had higher permeability than controls at T2 hyperintense WM lesions on DCE MR imaging. • mTBI patients with PCS had higher permeability than controls also at NAWM and predilection sites for DAI. • BBB disruption may be implicated in the development of PCS in mTBI patients.