Esophageal mast cells may be associated with the perception of symptoms in patients with eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is a type 2 helper T-cell (Th2)-mediated allergic disease that involves mast cells. This study aimed to clarify the relationship between perception of symptoms and mast cell levels in patients with EoE. METHODS: We enrolled patients with asymptomatic esophageal eosinophilia (aEE) and those with symptomatic EoE. Immunofluorescence staining was performed on esophageal biopsy specimens to quantify mast cell-related molecules, such as tryptase, proteinase-activated receptor (PAR)-2, and vasoactive intestinal peptide receptor (VPAC)-1. RESULTS: We evaluated 28 and 58 patients with aEE and EoE, respectively. There were no significant differences in clinical and endoscopic features and peak eosinophil counts between both groups. Mast cell tryptase-positive areas were significantly higher in EoE than in aEE (4.9 [3.5-6.2] vs. 2.0 [1.2-3.4] %, p < 0.01). The number of PAR-2-positive cells was significantly higher in EoE than in aEE (14 [8.8-20.0] vs. 4 [2.8-8.0] cells/high-power field [HPF], p < 0.01). The number of VPAC-1-positive cells was significantly higher in the EoE group than in the aEE group (13 [8.8-16.0] vs. 6 [3.0-9.3] cells/HPF, p < 0.01). A positive correlation was observed between the numbers of PAR-2-positive cells and VPAC-1-positive cells (r = 0.851, p < 0.01). Moreover, mast cell tryptase-positive areas positively correlated with the number of PAR-2- and VPAC-1-positive cells (r = 0.352, p < 0.01; r = 0.355, p < 0.01, respectively). CONCLUSIONS: Esophageal mast cells and their receptors, PAR-2 and VPAC-1, may contribute to the perception of symptoms in patients with EoE.

Lifestyle changes during the coronavirus disease 2019 pandemic impact metabolic dysfunction-associated fatty liver disease.

BACKGROUND AND AIMS: The coronavirus disease 2019 (COVID-19) pandemic precipitated lifestyle changes. We aimed to clarify whether COVID-19-induced lifestyle changes affected the development of metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS: This retrospective longitudinal study included 973 participants who underwent health check-ups between 2018 and 2020. We used data from the MedCity21 health examination registry. Participants' clinical characteristics and lifestyle habits were investigated. Independent lifestyle predictors of MAFLD development before the pandemic (2018-2019) and during the pandemic (2019-2020) were identified using logistic regression analysis. RESULTS: In 2018, 261 (27%) patients were diagnosed with MAFLD. Before the pandemic, 22 patients developed new MAFLD. During this time, routine late-night meals were identified as an independent lifestyle predictor of MAFLD development (hazard ratio [HR] 2.54, 95% confidence interval [CI] 1.02-6.36, P = .046). In contrast, 44 patients developed new MAFLD during the pandemic. During this time, higher daily alcohol intake was identified as an independent lifestyle predictor of MAFLD development (HR 1.03, 95% CI 1.01-1.05, P = .008). In participants aged <60 years, daily alcohol intake and the proportion of participants who ate 2 times/day were significantly higher in patients who developed MAFLD during the pandemic than in those who did not. In participants aged ≥60 years, no lifestyle habits were associated with MAFLD development before or during the pandemic. CONCLUSIONS: New MAFLD diagnoses increased during the COVID-19 pandemic. Changes in lifestyle factors, particularly in those aged <60 years, must be monitored and addressed as the pandemic continues.

Structural Dynamic Heterogeneity of Polyubiquitin Subunits Affects Phosphorylation Susceptibility.

Polyubiquitin is a multifunctional protein tag formed by the covalent conjugation of ubiquitin molecules. Due to the high rigidity of the ubiquitin fold, the ubiquitin moieties in a polyubiquitin chain appear to be structurally equivalent to each other. It is therefore unclear how a specific ubiquitin moiety in a chain may be preferentially recognized by some proteins, such as the kinase PINK1. Here we show that there is structural dynamic heterogeneity in the two ubiquitin moieties of K48-linked diubiquitin by NMR spectroscopic analyses. Our analyses capture subunit-asymmetric structural fluctuations that are not directly related to the closed-to-open transition of the two ubiquitin moieties in diubiquitin. Strikingly, these newly identified heterogeneous structural fluctuations may be linked to an increase in susceptibility to phosphorylation by PINK1. Coupled with the fact that there are almost no differences in static tertiary structure among ubiquitin moieties in a chain, the observed subunit-specific structural fluctuations may be an important factor that distinguishes individual ubiquitin moieties in a chain, thereby aiding both efficiency and specificity in post-translational modifications.

Exosomal hsa-miR-933 in Gastric Juice as a Potential Biomarker for Functional Dyspepsia.

BACKGROUND: MicroRNAs (miRNAs) in exosomes represent disease-specific profiles and are applied as biomarkers in oncology. However, in functional dyspepsia (FD), the role of exosomal miRNAs has not been fully elucidated. AIMS: To investigate exosomal miRNAs as potential biomarkers of FD using liquid biopsy. METHODS: This retrospective cohort study included 11 subjects with FD and 11 age- and sex-matched healthy controls (HCs). We collected gastric juice and isolated exosomal miRNAs. In a discovery cohort, expression levels of 2565 miRNAs were evaluated by 3D-Gene® microarray. miRNA expression profiles from exosomes of subjects with FD and HCs were compared by two normalization methods: (1) global normalization and (2) normalization by internal control. Subsequently, in a validation cohort, the expression levels of miRNAs were validated by quantitative reverse transcription PCR (RT-qPCR). RESULTS: Through microarray analysis using the two methods, we identified 39 miRNAs that were consistently and significantly downregulated in FD cases compared with those in HCs. Of these, 12 miRNAs (hsa-miR-933, hsa-miR-345-5p, hsa-miR-708-5p, hsa-miR-203a-3p, hsa-miR-619-5p, hsa-miR-4294, hsa-miR-4481, hsa-miR-196a-5p, hsa-miR-3918, hsa-miR-372-3p, hsa-miR-658, and hsa-miR-3654) were further validated by RT-qPCR. Our results indicated that hsa-miR-933 was significantly downregulated in FD compared with HCs (0.317 ± 0.205-fold, P = 0.0317). Furthermore, the expression level of hsa-miR-933 was negatively associated with dyspepsia score and the frequency of epigastric pain and/or burning (P < 0.01, r = - 0.835; P = 0.0280, r = - 0.688, respectively). CONCLUSIONS: Exosomal hsa-miR-933 in gastric juice could be a candidate biomarker for FD.

[A case of excessive supragastric belching treated with cognitive behavioral therapy].

A 52-year-old woman had a 6-month history of frequent belching;however, esophagogastroduodenoscopy revealed no abnormal findings. She presented to our department with belching refractory to several medications. Abdominal radiography revealed no massive gas in the stomach and intestine. She had frequent belching during the medical interview but no belching during speaking. Findings from high-resolution esophageal manometry and esophageal impedance pH monitoring confirmed supragastric belching. Thus, she was diagnosed as having excessive supragastric belching, which improved with cognitive behavioral therapy.

Barrett's esophagus is negatively associated with eosinophilic esophagitis in Japanese subjects.

BACKGROUND: Although both eosinophilic esophagitis (EoE) and Barrett's esophagus (BE) are considered to be associated with T helper (Th) 2-mediated immune responses, the association between EoE and BE is unclear. We investigated the clinical relationship between EoE and BE. METHODS: We conducted a single-center retrospective observational study. The study included 95 patients with EoE and randomly selected age- and sex-matched controls who underwent esophagogastroduodenoscopy during a medical health check-up at Osaka City University in a ratio of 1:2 for comparison. We compared the clinical characteristics and the prevalence rate of BE, reflux esophagitis (RE), hiatal hernia, and atrophic gastritis between EoE patients and controls by univariate analysis. Furthermore, we performed multivariate logistic regression analysis to investigate the association of these factors with EoE. RESULTS: On univariate analysis, the prevalence rate of BE was significantly lower in patients with EoE than in controls (2.1% vs. 13.2%; p = 0.00528). In contrast, the prevalence rate of RE was higher in EoE patients than in controls, but it was not statistically significant (absence and Grades A, B, and C: 74.7%, 18.9%, 5.3%, and 1.1% vs. 83.7%, 12.6%, 3.7%, and 0%; p = 0.193, respectively). Multivariate analysis showed that BE was negatively associated with EoE (odds ratio: 0.132; 95% confidence interval: 0.0302-0.573; p = 0.00686). CONCLUSIONS: BE is negatively associated with EoE in Japanese subjects. The mechanism behind the inverse relationship between EoE and BE should be examined.

2,3-Butanediol production from cellobiose using exogenous beta-glucosidase-expressing Bacillus subtilis.

We engineered efficient 2,3-butanediol (23BD) production from cellobiose using Bacillus subtilis. First, we found that B. subtilis harboring an empty vector could produce 23BD from cellobiose. However, productivity using cellobiose as a carbon source was lower than that when using glucose. This lower productivity was improved by adding purified beta-glucosidase from Thermobifida fusca YX (Tfu_0937) in the fermentation. Encouraged by these findings, we found that hydrolysis of cellobiose to glucose was an important reaction of 23BD biosynthesis in B. subtilis using cellobiose. Hence, we created efficient 23BD production from cellobiose using exogenous Tfu_0937-expressing B. subtilis. Using the engineered strain, 21.2 g L(-1) of 23BD was produced after 72 h of cultivation. The productivity and yield were 0.294 g L(-1) h(-1) and 0.35 g 23BD/g cellobiose, respectively. We successfully demonstrated efficient 23BD production from cellobiose by using BGL-expressing B. subtilis.

Kinematic characteristics of the scapula and clavicle during military press exercise and shoulder flexion.

BACKGROUND: The military press is an exercise frequently prescribed for scapular and shoulder rehabilitation. Although this exercise has previously been analyzed by electromyography, its kinematic features remain poorly understood. In this study, we aimed to clarify these features of the military press and suggest relevant clinical applications. METHODS: Sixteen healthy men participated in this study. The participants performed the military press while holding 2 kg weights, as well as shoulder flexion with and without 2 kg weights, and an electromagnetic motion capture system was used to analyze the kinematic features of the scapula, clavicle, and humerus during these exercises. The motions of the scapula and clavicle were analyzed at 10° increments of shoulder flexion from 30° to 120°. RESULTS: The military press involved less scapular internal rotation, greater upward rotation, and greater posterior tilt than shoulder flexion with or without weights, especially in the starting to middle range of shoulder flexion. Greater clavicular retraction and elevation were also seen during the military press. DISCUSSION: The movements of the scapula and clavicle during the military press differ significantly from those during shoulder flexion with and without weights. The kinematic features of the military press, which involved less scapular internal rotation, greater upward rotation, and greater posterior tilt than did shoulder flexion, may make it a useful re-education exercise (if pain allows) for patients with decreased scapular external rotation, upward rotation, and posterior tilting. The results of this study might provide a kinematic basis for the use of this widely performed shoulder exercise.

Superficial oesophageal mucosal innervation may contribute to severity of symptoms in oesophageal motility disorders.

BACKGROUND: Mechanisms underlying perception of dysphagia and chest pain have not been completely elucidated, although oesophageal mucosal afferent nerves might play an important role. AIMS: To evaluate the relationship between oesophageal mucosal afferent nerves and the severity of dysphagia and chest pain in oesophageal motility disorders. METHODS: We prospectively recruited patients with oesophageal motility disorders having dysphagia and/or chest pain from whom oesophageal biopsies were obtained. High-resolution manometry classified patients into disorders of oesophagogastric junction (OGJ) outflow and disorders of peristalsis. Symptom severity was assessed using validated questionnaires including Brief Oesophageal Dysphagia Questionnaire (BEDQ). Immunohistochemistry was performed on oesophageal biopsies to evaluate the location of calcitonin gene-related peptide (CGRP)-immunoreactive mucosal afferent nerves. Findings were compared to existing data from 10 asymptomatic healthy volunteers. RESULTS: Of 79 patients, 61 patients had disorders of OGJ outflow and 18 had disorders of peristalsis. CGRP-immunoreactive mucosal nerves were more superficially located in the mucosa of patients with oesophageal motility disorders compared to healthy volunteers. Within disorders of OGJ outflow, the location of CGRP-immunoreactive nerves negatively correlated with BEDQ score both in the proximal (ρ = -0.567, p < 0.001) and distal oesophagus (ρ = -0.396, p = 0.003). In the proximal oesophagus, strong chest pain was associated with more superficially located mucosal nerves than weak chest pain (p = 0.04). Multivariate analysis showed superficial nerves in the proximal oesophagus was independently associated with severe dysphagia in disorders of OGJ outflow (p = 0.008). CONCLUSIONS: Superficial location of mucosal nerves in the proximal oesophagus might contribute to symptoms, especially severe dysphagia, in disorders of OGJ outflow.

The FibroScan-aspartate aminotransferase score can stratify the disease severity in a Japanese cohort with fatty liver diseases.

This study aimed to prove that the FibroScan-aspartate aminotransferase (FAST) scores can be used to stratify disease severity in a Japanese cohort with fatty liver diseases [metabolic dysfunction-associated fatty liver disease (MAFLD) and nonalcoholic fatty liver disease (NAFLD)]. All the participants (n = 2254) underwent liver stiffness measurements and controlled attenuation parameter assessments. We compared the clinical characteristics of the patients with MAFLD and NAFLD using the FAST scores and explored the independent determinants of FAST scores ≥ 0.35, which indicated possible progressive disease. Overall, MAFLD was diagnosed in 789 patients (35.0%), while NAFLD was diagnosed in 618 (27.4%). The proportion of patients that had a condition that suggested progressive liver disease was higher in those with MAFLD than in those with NAFLD [68 (8.6%) vs 48 (7.7%)]. The area under the receiver-operating characteristic curve of the FAST score for diagnosing advanced fibrosis was 0.969 in MAFLD and 0.965 in NAFLD. Multivariate analyses determined that diabetes mellitus, alanine aminotransferase (ALT) levels, fatty liver index, and Fibrosis-4 index independently predict FAST scores ≥ 0.35 in patients with MAFLD. ALT levels had the strongest correlation with the FAST scores (p = 0.7817). The FAST score could stratify the disease severity in the Japanese cohort with fatty liver diseases.

Validation of a two-step approach combining serum biomarkers and liver stiffness measurement to predict advanced fibrosis.

BACKGROUND AND AIM: The Gut and Obesity in Asia Workgroup recently reported that a two-step approach using fibrosis scores followed by liver stiffness measurement (LSM) could accurately detect patients with non-alcoholic fatty liver disease (NAFLD) having advanced fibrosis in low-risk fibrosis populations. This study aimed to validate the utility of this approach using a Japanese health checkup registry. METHODS: This cross-sectional study included subjects who underwent a health checkup from 2014 to 2019. Using estimated fibrosis stage measured by LSM as a standard, we calculated the percentage of misclassification from assessments made based on fibrosis scores (NAFLD fibrosis score [NFS] or Fibrosis-4 score [FIB-4]) and LSM, alone or in combination. RESULTS: Of 630 subjects with NAFLD, 4 (0.8%) had advanced fibrosis. In the first-step evaluation, only 21.4-38.0% of subjects needed further testing. This approach was associated with a high specificity of approximately 100% and a negative predictive value of 99.7%. The percentage of misclassification based on NFS or FIB-4 values followed by LSM in all subjects and using LSM after NFS or FIB-4 determination only in subjects with indeterminate/high NFS or FIB-4 values (two-step approach) was 0% and 0.3% and 0.16% and 0.3%, respectively. In addition, very few false negatives occurred for both NFS and FIB-4. CONCLUSION: The two-step approach helps to identify the subjects with NAFLD who have advanced fibrosis during a routine health checkup and is associated with only a few false negatives.

A mask-based infection control method for screening endoscopy may prevent SARS-CoV-2 transmission and relieve staff anxiety.

OBJECTIVES: Endoscopy confers high risk for acquiring coronavirus disease 2019. Although guidelines recommend that medical staff use personal protective equipment, no infection control equipment have been established for patients. This study aimed to clarify the usefulness of two face masks we had designed for transnasal and transoral endoscopy. METHODS: The efficacy of the masks was evaluated by simulating coughing in a mannequin with fluorescent dyes and mapping the droplet trajectory and number. The number of aerosols generated during endoscopy was clinically evaluated in the endoscopy room. Overall, 4356 screening endoscopies were performed with the patients wearing our masks at Medcity21, a health checkup facility, between June and December 2020; the effects of the masks on the patient's condition were evaluated retrospectively. An 11-item paper-based survey was performed by the endoscopy staff 6 months after the adoption of the mask-based infection control method. RESULTS: Use of both masks reduced the number of droplets released during the simulation. Clinically, the use of both masks did not affect the patients' conditions during endoscopy and prevented an increase in the aerosols in the endoscopy room. This mask-based infection control method was favorably received, and all staff indicated that understanding the efficacy of our mask-based infection control reduced their anxiety regarding infection. Until December 2020, none of our staff had contracted SARS-CoV-2. CONCLUSION: Our mask-based infection control method is easy to adopt, inexpensive, and effective; understanding its effectiveness may help ease the fear of infection among endoscopy staff.

[A case of superficial siderosis with repeated episodes of epilepsy].

We report a patient with superficial siderosis that repeated episodes of epilepsy. The patient was a 62-year-old male, and underwent an operation for the tumor of the spinal cord at 22 years of age. He had become deaf at 50 years of age, and repeated loss of consciousness at 59 years of age and later. Neurological examination revealed cerebellar ataxia and bilateral sensorineural deafness in addition to paraplegia, which was caused by the spinal cord tumor. Brain MRI showed low intensity rim around the brain stem, cerebellar hemisphere, and inferior aspects of the temporal and frontal lobes, being consistent with superficial siderosis. Hemosiderin deposition for an extended period was considered to contribute to the pathogenesis of epilepsy.

Proton pump inhibitors enhance intestinal permeability via dysbiosis of gut microbiota under stressed conditions in mice.

BACKGROUND: Intestinal permeability and psychological stress are considered the key mechanism(s) in functional dyspepsia (FD). Although proton pump inhibitors (PPIs) are commonly used for the treatment of FD, the effect of PPIs on intestinal permeability has not been elucidated. This study investigated the effect of PPI on intestinal permeability under stressed conditions. METHODS: C57BL/6J mice were subjected to water avoidance stress (WAS) and administered rabeprazole (40 mg/kg) or vehicle treatment (VT). We then evaluated intestinal permeability both in vivo and ex vivo using plasma fluorescein isothiocyanate-dextran and by assessing the paracellular permeability and transepithelial electrical resistance (TEER) in an Ussing chamber, respectively. Furthermore, we evaluated the effect of PPI-treated fecal microbiota transplant (FMT) on intestinal permeability in vivo. Microbiota profiles of donor feces were assessed by 16S rRNA gene analysis using MiSeq and QIIME2. KEY RESULTS: In the WAS treatment, PPI significantly enhanced intestinal permeability in vivo compared to that in VT. Moreover, PPI significantly increased paracellular permeability and decreased TEER in the duodenum and jejunum, respectively, compared to those in VT under stressed conditions. Moreover, both vasoactive intestinal peptide (VIP) receptor antagonist and ketotifen significantly reversed the effect of PPI on intestinal permeability. Furthermore, PPI-treated FMT significantly increased the intestinal permeability in vivo compared to that in vehicle-treated FMT. Proton pump inhibitors treatment altered the gut microbiota composition, indicating that PPI induced dysbiosis. CONCLUSIONS AND INFERENCES: Under stressed conditions, PPI enhances intestinal permeability via dysbiosis of gut microbiota. Vasoactive intestinal peptide and mast cells are also implicated in the underlying mechanisms.

Supragastric belching in Japan: lower prevalence and relevance for management of gastroesophageal reflux disease compared to United Kingdom.

BACKGROUND: Supragastric belching (SGB) may play a role in the pathophysiology of proton pump inhibitors (PPIs)-refractoriness in gastroesophageal reflux disease (GERD). SGB may be present in up to 40% of reflux symptoms in PPI-refractory GERD. Most reports on SGB have come from Western countries, and little is known about the prevalence and relevance of SGB in Asian refractory GERD patients. This study aimed at comparing the role of SGB in GERD patients in Japan and the UK. METHODS: We re-analyzed impedance-pH monitoring tracings from patients who were referred to tertiary centers in Japan and the UK due to PPI-refractory reflux symptoms. The prevalence of excessive SGB and the impact of SGB on reflux symptoms were compared between the two countries. RESULTS: Impedance-pH tracings from124 Japanese and 83 British patients were re-analyzed. Japanese patients were significantly younger and had smaller body mass index than the British (P < 0.001). Japanese patients had significantly lower prevalence of excessive SGB (18.5%) than the UK (36.1%) irrespective of reflux phenotype (P = 0.006). Logistic regression analysis showed that the geographical/cultural difference was the only factor associated with the different prevalence of SGB (odds ratio; 2.91, 95% CI 1.09-7.73, P = 0.032). SGB were related to typical reflux symptoms very rarely in Japan [0% (0-4.9)] compared to the UK [35% (0-54.1)] (P = 0.071). CONCLUSIONS: The prevalence of SGB and their impact on reflux symptoms is significantly lower in Japan compared to the UK. The difference is not related to reflux parameters but might come from ethnic/cultural factors to be further characterized.

Hydrogen-Deuterium Exchange Profiles of Polyubiquitin Fibrils.

Ubiquitin and its polymeric forms are conjugated to intracellular proteins to regulate diverse intracellular processes. Intriguingly, polyubiquitin has also been identified as a component of pathological protein aggregates associated with Alzheimer's disease and other neurodegenerative disorders. We recently found that polyubiquitin can form amyloid-like fibrils, and that these fibrillar aggregates can be degraded by macroautophagy. Although the structural properties appear to function in recognition of the fibrils, no structural information on polyubiquitin fibrils has been reported so far. Here, we identify the core of M1-linked diubiquitin fibrils from hydrogen-deuterium exchange experiments using solution nuclear magnetic resonance (NMR) spectroscopy. Intriguingly, intrinsically flexible regions became highly solvent-protected in the fibril structure. These results indicate that polyubiquitin fibrils are formed by inter-molecular interactions between relatively flexible structural components, including the loops and edges of secondary structure elements.

Effects of trunk rotation on scapular kinematics and muscle activity during humeral elevation.

Trunk rotation often accompanies humeral elevation, during daily activities as well as sports activities. Earlier studies have demonstrated that changes in spinal posture contribute to scapular motion during humeral elevation. However, the effect of trunk rotation on scapular kinematics during humeral elevation has received scant attention. This study aimed to clarify how trunk rotation affects scapular kinematics and muscle activities during humeral elevation. Electromagnetic motion capture and electromyography were used to assess scapular and clavicular motion and muscle activity in the right and left sides of 12 healthy young men. The subjects were seated and instructed to elevate both arms with the trunk in neutral, ipsilaterally rotated, or contralaterally rotated position. Ipsilaterally rotated trunk position decreased the internal rotation (by 5°, relative to neutral trunk position) and increased the upward rotation (by 4°, relative to neutral trunk position) of the scapula. Trunk position did not affect clavicular motion during humeral movement. Electromyography showed that contralaterally rotated trunk position increased the activity of the upper trapezius and serratus anterior muscles and decreased the activity of the lower trapezius. Therapists should consider the importance of trunk rotation, which may be the key to developing more efficient rehabilitation programs.

Global aphasia without hemiparesis: the underlying mechanism examined by transcranial magnetic stimulation.

INTRODUCTION: Global aphasia without hemiparesis (GAWH) is a rare stroke syndrome. Using transcranial magnetic stimulation (TMS), we evaluated 2 possible pathogenic mechanisms for GAWH: sparing of the decussated pyramidal tract, or alternatively, compensation by the ipsilateral pyramidal tract. METHODS: Six patients were diagnosed to have GAWH by the Standard Language Test of Aphasia for Japanese. All patients underwent brain magnetic resonance (MR) imaging and angiography. According to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria, stroke subtype was determined as 3 patients with cardioembolic stroke, 2 with large-artery atherosclerosis, and 1 with another type. All patients underwent TMS, using a figure-of-8 coil, from 3 to 12 months after the onset, and motor evoked potentials were recorded on the abductor digiti minimi muscles. RESULTS: All patients had left-sided frontal or temporal lesions that were confirmed by MR diagnostic imaging. No motor evoked potential could be recorded by ipsilateral TMS. In 3 patients, brain stimulation on either side evoked the same amplitude on the contralateral abductor digiti minimi, whereas in the other 3 patients, the amplitude was suppressed on the right side. The infarction in the former patients was caused by cardioembolism and in the latter was not. In serial slices of brain MR imaging, the pyramidal tract was spared in the former and was involved to various degrees in the latter 3 patients. CONCLUSIONS: We recommend that GAWH was caused by the sparing of the decussated pyramidal tract. The pyramidal tract was intact in cases of GAWH caused by cardioembolism and subclinically impaired by other causes.