High frequency of HTRA1 AND ABCC6 mutations in Japanese patients with adult-onset cerebral small vessel disease.

BACKGROUND: This study aimed to clarify the frequency and clinical features of monogenic cerebral small vessel disease (mgCSVD) among patients with adult-onset severe CSVD in Japan. METHODS: This study included patients with adult-onset severe CSVD with an age of onset ≤55 years (group 1) or >55 years and with a positive family history (group 2). After conducting conventional genetic tests for NOTCH3 and HTRA1, whole-exome sequencing was performed on undiagnosed patients. Patients were divided into two groups according to the results of the genetic tests: monogenic and undetermined. The clinical and imaging features were compared between the two groups. RESULTS: Group 1 and group 2 included 75 and 31 patients, respectively. In total, 30 patients had NOTCH3 mutations, 11 patients had HTRA1 mutations, 6 patients had ABCC6 mutations, 1 patient had a TREX1 mutation, 1 patient had a COL4A1 mutation and 1 patient had a COL4A2 mutation. The total frequency of mutations in NOTCH3, HTRA1 and ABCC6 was 94.0% in patients with mgCSVD. In group 1, the frequency of a family history of first relatives, hypertension and multiple lacunar infarctions (LIs) differed significantly between the two groups (monogenic vs undetermined; family history of first relatives, 61.0% vs 25.0%, p=0.0015; hypertension, 34.1% vs 63.9%, p=0.0092; multiple LIs, 87.8% vs 63.9%, p=0.0134). CONCLUSIONS: More than 90% of mgCSVDs were diagnosed by screening for NOTCH3, HTRA1 and ABCC6. The target sequences for these three genes may efficiently diagnose mgCSVD in Japanese patients.

Characteristics of sagittal spinopelvic alignment in patients with Parkinson's disease presenting with dropped head syndrome: a case series study.

BACKGROUND: Dropped head syndrome (DHS) is a rare specific abnormal posture known to develop in Parkinson's disease (PD). This case series study aimed to characterize DHS by analyzing the characteristics of sagittal spinopelvic alignment in patients with PD/DHS. METHODS: The study included eight patients with PD/DHS (men = 3, women = 5; mean age, 68.1 ± 6.4 years). Sagittal spinopelvic alignment was evaluated using 10 parameters on whole-spine lateral radiographs. RESULTS: The time from the onset of PD to that of DHS varied among the patients from 0 to 15.3 years. In three patients, DHS appeared before the diagnosis of PD. The severity of motor symptoms at DHS onset varied from modified Hoehn and Yahr stage 1 to 4 among the patients. Although the spinopelvic parameters differed among PD/DHS individuals, all patients exhibited cervical kyphosis (cervical lordosis < 0˚). In patients with a larger T1 slope and greater thoracic kyphosis, anterocollis tended to be more severe. According to the assessment of the sagittal vertical axis (SVA), half of the patients showed a positive SVA (SVA ≥ 0 mm), whereas the other half showed a negative SVA (SVA < 0 mm). CONCLUSION: DHS appeared regardless of the duration or severity of PD. Although all patients with PD/DHS exhibited cervical kyphosis, the C7 plumb line was shifted anteriorly in half of the patients and posteriorly in the other half.

High-risk patent foramen ovale and elderly in cryptogenic stroke.

BACKGROUND: High-risk patent foramen ovale (PFO) could be pathological in cryptogenic stroke (CS), but its clinical characteristics have not been fully studied, especially in elderly patients. METHODS: Patients with CS were enrolled in the CHALLENGE ESUS/CS registry, a multicenter registry of CS patients undergoing transesophageal echocardiography. Clinical characteristics were compared among three groups: high-risk PFO group, large shunt PFO (≥25 microbubbles) or PFO with atrial septal aneurysm (ASA); right-to-left shunt (RLS) group, RLS including PFO with <25 microbubbles or without ASA; and no-RLS group. RESULTS: In total, 654 patients were analyzed: 91, 221, and 342 in the high-risk PFO, RLS, and no-RLS groups, respectively. In multinomial logistic regression analysis, the male sex (odds ratio [OR] 1.825 [1.067-3.122]) was independently associated with high-risk PFO, but hypertension (OR, 0.562 [0.327-0.967]), multiple infarctions (OR, 0.601 [0.435-0.830]), and other cardioaortic embologenic risks (OR, 0.514 [0.294-0.897]) were inversely associated with high-risk PFO compared with non-RLS. In 517 patients aged ≥60 years, multiple infarctions (OR, 0.549 [0.382-0.788]) and other cardioaortic embologenic risks (OR, 0.523 [0.286-0.959]) were inversely associated with high-risk PFO. CONCLUSIONS: High-risk PFO had specific clinical characteristics and possible mechanistic associations, and this trend was consistent among CS patients aged ≥60 years. CLINICAL TRIAL REGISTRATION INFORMATION: http://www.umin.ac.jp/ctr/ (UMIN000032957).

Characteristics of sagittal spinopelvic alignment in patients with Parkinson's disease.

INTRODUCTION: The aim of this study was to characterize the associations between sagittal spinopelvic alignment and motor symptoms in patients with Parkinson's disease (PD). METHODS: The study included patients with idiopathic PD (aged <80 years and with abnormal posture). All patients underwent whole-spine lateral and coronal radiography. Sagittal spinopelvic alignment was evaluated using nine parameters. Motor symptoms were evaluated using the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score-with bradykinesia and axial motor sub-scores. Multivariate analysis was used to analyze associations between motor symptoms and sagittal spinopelvic alignment in PD patients according to sex. RESULTS: The study subjects were 79 PD patients (39 men, 40 women; median age, 70 years). Clear sex-related differences were noted. In male patients, the MDS-UPDRS part III score correlated significantly with cervical sagittal vertical axis (SVA), and bradykinesia and axial motor scores correlated significantly with SVA, cervical SVA, and T1 slope. In female patients, the MDS-UPDRS part III score correlated significantly with thoracic kyphosis, bradykinesia score correlated significantly with cervical SVA and thoracic kyphosis, and the axial motor score correlated significantly with SVA, cervical SVA, T1 slope, sacral slope, and pelvic tilt. CONCLUSION: Our results showed clear correlations among various motor symptoms and sagittal global alignment in PD patients and that these correlations are different in female PD patients and their male counterparts.

Impact of the catechol-O-methyltransferase Val158Met polymorphism on the pharmacokinetics of L-dopa and its metabolite 3-O-methyldopa in combination with entacapone.

In the pharmacotherapy of patients with Parkinson's disease (PD), entacapone reduces the peripheral metabolism of L-dopa to 3-O-methyldopa (3-OMD), thereby prolonging the half-life (t1/2) of L-dopa and increasing the area under the concentration curve (AUC). The effect of entacapone on the pharmacokinetics of L-dopa differs between patients with high-activity (H/H) and low-activity (L/L) catechol-O-methyltransferase (COMT) Val158Met polymorphisms, but the effects are unclear in heterozygous (H/L) patients. 3-OMD has a detrimental effect and results in a poor response to L-dopa treatment in patients with PD; however, the influence of this polymorphism on the production of 3-OMD remains unknown. Therefore, the present study aimed to clarify the effect of the COMT Val158Met polymorphism on the concentrations of L-dopa and 3-OMD in the presence of entacapone. We performed an open-label, single-period, single-sequence crossover study at two sites in Japan. The study included 54 Japanese patients with PD, who underwent an acute L-dopa administration test with and without 100 mg entacapone on two different days. Entacapone increased L-dopa AUC0-infinity by 1.59 ± 0.26-fold in the H/H group, which was significantly higher than that in the H/L (1.41 ± 0.36-fold) and L/L (1.28 ± 0.21-fold) groups (p < 0.05). The concurrent administration of L-dopa with entacapone suppressed the increase in 3-OMD levels compared with L-dopa alone in all genotypes. Our results suggest that the COMT Val158Met polymorphism may be an informative biomarker for individualized dose adjustment of COMT inhibitors in the treatment of PD.

Analysis of non-invasive gait recording under free-living conditions in patients with Parkinson's disease: relationship with global cognitive function and motor abnormalities.

BACKGROUND: We investigated the gait characteristics of patients with Parkinson's disease (PD), under free-living conditions, using a wearable device, and assessed their relationships with global cognitive function and motor abnormalities. METHODS: The study subjects comprised patients with PD aged < 80 years, with a Mini-Mental State Examination (MMSE) score of ≥20, free of any motor complications. A wearable sensor with a built-in tri-axial accelerometer was waist-mounted on each patient, and continuous, 24-h records were obtained. The mean gait cycle duration and mean gait acceleration amplitude, under free-living conditions, were computed and analyzed to determine their relationship with disease duration, MMSE score, Unified Parkinson's Disease Rating Scale (UPDRS) Part III score, and postural instability and gait difficulty (PIGD) score. RESULTS: The study included 106 consecutive patients with PD. The mean gait cycle duration was 1.18 ± 0.12 s, which was similar to that of the normal controls. However, the mean gait acceleration amplitude of PD patients (1.83 ± 0.36 m/s2) was significantly lower than that of the control (p < 0.001). In PD patients, the mean gait acceleration amplitude correlated with the MMSE (ß = 0.197, p = 0.028), UPDRS Part III (ß = - 0.327, p < 0.001), and PIGD (ß = - 0.235, p = 0.008) scores. CONCLUSIONS: The gait rhythm of PD patients is preserved at levels similar to those of normal subjects. However, the mean gait acceleration amplitude was significantly reduced in patients with PD. The results indicate that gait acceleration amplitude correlates with the severity of motor disorders and global cognitive function.

Association of daily physical activity with cognition and mood disorders in treatment-naive patients with early-stage Parkinson's disease.

To determine the association of daily physical activity with cognition, mood disorders, and olfactory function in treatment-naive patients with early-stage Parkinson's disease (PD). The study subjects were 52 treatment-naive patients with early-stage PD (< 80 years). Daily physical activity was measured using a wearable sensor with a built-in triaxial accelerometer, and its association with cognition [mini-mental state examination (MMSE), clock-drawing test (CDT), frontal assessment battery (FAB), and behavioral assessment of the dysexecutive syndrome (BADS)], depressive symptoms [Beck Depression Inventory-Second Edition (BDI-II)], apathy [Starkstein Apathy Scale (AS)], and olfactory function [Odor Stick Identification Test for the Japanese (OSIT-J)] was analyzed using multiple linear regression after adjustment for age, sex, and education status. The daily physical activity (0.42 ± 0.11 m/s2) of the PD group was significantly lower than that of healthy controls (p < 0.001). Moreover, the daily physical activity of the PD group was significantly associated with FAB (ß = 0.337, p = 0.027) and BADS (ß = 0.374, p = 0.017) scores, but not with MMSE, CDT, BDI-II, AS, and OSIT-J scores. The daily physical activity is significantly reduced in treatment-naive patients with early-stage PD, and the low activity correlates with frontal/executive function.

Characteristics of apathy in treatment-naïve patients with Parkinson's disease.

INTRODUCTION: Although apathy is a common psychiatric symptom of Parkinson's disease (PD), there are many unknown aspects of its pathology. This study aimed to investigate the characteristics of apathy in treatment-naïve patients with early-stage PD. METHODS: Fifty treatment-naïve patients with early-stage PD were divided into 1 of 2 groups-apathetic or non-apathetic-based on Starkstein Apathy Scale (AS) scores. Cognitive function, depressive symptoms, olfactory function, and motor severity were compared between the two groups using validated assessment scales. Multiple linear regression was performed to assess the association between AS scores and clinical parameters. RESULTS: Apathy (AS score ≥16) was observed in 13 (26%) patients. Assessment scale scores (Beck Depression Inventory-Second Edition [p < .004]; modified Hoehn & Yahr stage [p = .039]; Unified Parkinson's Disease Rating Scale part III [p < .001]) were significantly higher in apathetic patients than in non-apathetic patients. Significant association between these scale scores and AS score was also evident (all p ≤ .001). There were no significant differences in the test scores derived from several other validated scales. CONCLUSION: Apathy was observed in 26% of treatment-naïve patients with early-stage PD. Significant association between apathy and motor severity was found, suggesting that dysfunction of the dopaminergic pathway is involved in the pathology of apathy.

Autopsy-proven case of paraneoplastic lower motor neuron disease with sensorimotor neuropathy due to Waldenström's macroglobulinemia.

We report a case of a male patient with a 19-year history of monoclonal and later polyclonal gammopathy who subsequently developed tetraparesis, bulbar palsy, and respiratory failure. Autopsy findings showed degeneration of the hypoglossal nuclei, prominent neuronal loss and atrophy in the anterior horn of the whole spinal cord despite the presence of mild astrocytosis, degeneration of the gracilis on one side, and infiltration of inflammatory cells, which included B cells and plasma cells in the anterior and posterior roots of the lumbar spinal cord, iliopsoas muscle, and perivascular area of the cervical cord. On immunostaining, cytoplasmic inclusions of phosphorylated transactivation response DNA-binding protein of 43 kDa were observed in the motor neurons and astrocytes of the hypoglossal nuclei and whole spinal cord. The final diagnosis was paraneoplastic lower motor neuron disease with sensorimotor neuropathy due to Waldenström's macroglobulinemia.

Progression level of extracapsular spread and tumor budding for cervical lymph node metastasis of OSCC.

OBJECTIVES: The progression level of extracapsular spread (ECS) for cervical lymph node metastasis of oral squamous cell carcinoma (OSCC) was previously divided into three types, and their relationships with the prognosis of patients were re-examined. PATIENTS AND METHODS: The Kaplan-Meier method was used to examine overall survival (OS) and relapse-free survival (RFS) curves. Prognosis factor for recurrence was analyzed with univariate and multivariate analysis. RESULTS: ECS was detected in 216 cases of OSCC and analyzed. The 5-year overall survival and RFS rates of patients with type C, which was microscopically defined as tumor invasion to perinodal fat or muscle tissue, were significantly poor at 40.6 and 37.8%, respectively. The results of a univariate analysis suggested that the prognosis of ECS in OSCC patients is associated with its progression level, particularly type C. The 5-year RFS rate of type C with tumor budding was significantly poor at 31.5%. Type C with tumor budding correlated with local and regional recurrence as well as distant metastasis. In a multivariate analysis, tumor budding was identified as an independent prognostic factor. CONCLUSIONS: These results suggest that the progression level of ECS and tumor budding are useful prognostic factors in OSCC patients. CLINICAL RELEVANCE: This study indicated that the progression level and tumor budding of ECS for cervical lymph node metastasis were useful prognostic factors in OSCC patients.

Secondary parkinsonism.

Although many disorders are included in secondary parkinsonism, the mechanisms underlying parkinsonism vary and have yet to be elucidated. Herein, we introduced a group of diseases included among the forms of secondary parkinsonism and provide overviews of clinically significant drug-induced parkinsonism (DIP), vascular parkinson- ism (VP), and idiopathic normal pressure hydrocephalus (iNPH) with a focus on pathophysiology and symptoms. Although DIP has the highest frequency among the forms of secondary parkinsonism, it is overlooked in many patients due to lack of knowledge about drugs by the prescribing physicians. Both VP and iNPH present with "lower body parkinsonism, " showing the characteristic gait disturbance. DIP and iNPH are treatable, highlighting the importance of early diagnosis and treatment intervention.

Kinematic analysis of 24-hour recording of walking pattern in patients with vascular parkinsonism.

BACKGROUND: There is a need to define the basic characteristics of various kinematic parameters recorded during walking in patients with vascular parkinsonism (VP). The present study was designed to determine the kinematic features of walking in VP patients. For this purpose, gait acceleration and gait cycle were recorded continuously over 24-h period of daily living in VP patients, patients with Parkinson's disease (PD), and healthy subjects. METHODS: We used our newly developed 24-h monitoring device, the portable gait rhythmogram, which records gait during walking, and computes gait-induced accelerations with pattern matching algorithm. We studied nine VP patients with history of multiple lacunar infarcts (mean age ± standard deviation (SD): 72.6 ± 5.0 years, 7 men), 39 PD patients (mean age ± SD: 70.8 ± 5.8 years, 18 women), and 15 normal control subjects (mean age ± SD: 67.9 ± 4.7 years, 9 men). RESULTS: The "amount of overall movements per 24 h" was lower in VP and PD, compared with the control, with no significant differences between the two groups. Gait acceleration during walking was significantly lower (p < 0.01 in each case), while the gait cycle was the same in VP and PD patients compared with the control. CONCLUSIONS: The results suggest that deficit in force production and preservation of gait rhythm are common features of walking patterns in VP and PD patients.

A case of pathology-proven neuromyelitis optica spectrum disorder with Sjögren syndrome manifesting aphasia and apraxia due to a localized cerebral white matter lesion.

A woman with Sjögren syndrome manifesting as aphasia with a left deep cerebral white matter lesion tested positive for anti-aquaporin 4 (AQP4) antibody. Open biopsy of the lesion revealed active demyelination with edematous changes and the preservation of most axons, indicating a non-necrotic demyelinating lesion. Immunostaining for AQP4 was diffusely lost, whereas the loss of glial fibrillary acidic protein immunostaining was limited but with highly degenerated astrocytic foot processes in perivascular areas. These results suggested neuromyelitis optica spectrum disorder (NMOSD) pathology rather than Sjögren-related vasculitis. Only cerebral cortical symptoms with a cerebral white matter lesion could be observed in NMOSDs.

Cerebral microbleeds and asymptomatic cerebral infarctions in patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a cardiac arrhythmia that does not infrequently induce ischemic strokes; however, little research has been reported on focal cerebral microangiopathic lesions in patients with AF. Recently cerebral microbleeds (CMBs) have been noticed for their potential implication in cerebral small vessel disease. Therefore, we had 2 goals in the present study: (1) to compare the prevalence of CMBs in patients with AF with that in patients without AF, and (2) to prove that CMBs could be a clinical predictive factor for the development of future cerebral microangiopathy in patients with AF without a history of symptomatic cerebral infarction in a prospective manner. METHODS: We performed yearly brain magnetic resonance imaging (MRI) assessments for a maximum of 5 years in 131 patients with AF and 112 control patients. Seventy-seven patients with AF underwent more than 3 yearly MRI scans. RESULTS: The Kaplan-Meier curve showed that the development of an asymptomatic cerebral infarction (ACI) was associated with the baseline presence of a CMB (P=.004). A multivariate Cox regression analysis revealed that the CMBs at baseline were significantly associated with an increment in not only the occurrence of ACIs (hazard ratio [HR], 5.414; 95% confidence interval [CI], 1.03-28.43; P=.046) but also in the consecutive development of CMBs (HR, 6.274; 95% CI, 1.43-27.56; P=.015). CONCLUSIONS: Patients with AF had a significantly higher prevalence of CMBs. The presence of CMBs in the baseline MRI may predict the consequent onset of an ACI and increase in CMBs in patients with AF.

Negative features of sporadic amyotrophic lateral sclerosis: Motor neurons of Onuf's nucleus survive in ADAR2-conditional knockout mice.

Patients with amyotrophic lateral sclerosis (ALS) do not develop oculomotor disturbances and vesicorectal dysfunction until end-stage disease owing to the survival of certain motor neurons (MNs), including oculomotor neurons and MNs within Onuf's nucleus. In sporadic ALS, adenosine deaminase acting on RNA 2 (ADAR2)-mediated editing of GluA2 mRNA at the Q/R site is compromised in lower MNs. We previously developed genetically modified mice with a conditional knockout of ADAR2 in cholinergic neurons (ADAR2flox/flox/VAChT-Cre, Fast; AR2). These mice displayed slow and progressive lower motor neuron death with TAR DNA-binding protein 43 (TDP-43) pathology, attributable to insufficient editing at the GluA2 Q/R site due to ADAR2 deficiency. MN death was more common in fast-fatigable MNs owing to differential vulnerability under conditions of ADAR2 deficiency. Although facial and hypoglossal nerves were impaired in AR2 mice, cell death did not occur within the oculomotor nerve nucleus, as observed in patients with sporadic ALS. Since the basis for avoiding cystorectal damage in ALS is unknown, we compared the features of Onuf's nucleus MNs in 12-month-old AR2 mice with those in age-matched wild-type mice. Although the number of MNs was not significantly lower in AR2 mice, the neurons exhibited a shrunken morphology and TDP-43 pathology. Onuf's nucleus MNs could survive in an ADAR2-deficient state and mainly included fast fatigue-resistant (FR) and slow (S) MNs. In summary, FR and S MNs show increased resilience to ADAR2 deficiency, potentially participating in an important neuronal death avoidance mechanism in ALS.

Morphometric analysis of spinal motor neuron degeneration in sporadic amyotrophic lateral sclerosis.

OBJECTIVES: This study aimed to clarify the relationship between 43-kDa TAR DNA-binding protein (TDP-43) pathology and spinal cord anterior horn motor neuron (AHMN) atrophy in sporadic amyotrophic lateral sclerosis (SALS). METHODS: Eight patients with SALS and 12 controls were included in this study. Formalin-fixed specimens of lumbar spinal cord samples were paraffin-embedded and sectioned at the level of the fourth lumbar spinal cord with a 4 µm thickness. Using a microscope, the long diameters of the neurons with nucleoli were measured in spinal AHMNs stained with an anti-SMI-32 antibody. AHMNs were divided into medial and lateral nuclei for statistical analysis. We also used previously reported data to measure the long diameter of AHMNs with initial TDP-43 pathology, in which TDP-43 was present both in the nucleus and cytoplasm. RESULTS: The long diameter of the lumbar spinal AHMNs in patients with SALS was smaller in the medial nucleus (42.54 ± 9.33 µm, n = 24) and the lateral nucleus (49.41 ± 13.86 µm, n = 129) than in controls (medial nucleus: 55.84 ± 13.49 µm, n = 85, p < 0.001; lateral nucleus: 62.39 ± 13.29 µm, n = 756, p < 0.001, Mann-Whitney U test). All 21 motor neurons with initial TDP-43 pathology were in the lateral nucleus, and their long diameter (67.60 ± 18.3 µm, p = 0.352) was not significantly different from that of controls. CONCLUSION: Motor neuron atrophy in SALS does not occur during the initial stages of TDP-43 pathology, and TDP-43 pathology is already advanced in the atrophied motor neurons.

The speed of completion of the decremental responses on repetitive nerve stimulation.

Objective: It is generally believed that the decremental response in repetitive nerve stimulation (RNS) stabilizes at the fourth or fifth response. We have a preliminary impression that the decremental response approaches a plateau earlier in proximal muscles than in distal muscles. We investigated the speed of the completion of the decremental response in different muscles. Methods: The "decrement completion ratio (DCR)" in the second or third response (DCR2 or DCR3) was defined as the ratio of the decremental percentage of the second or third response to that of the fourth response. Patients showing more than 10% decremental response both in the abductor pollicis (APB) and deltoid muscles were retrospectively extracted from our EMG database. The DCR2 and DCR3 were compared between two muscles in patients with myasthenia gravis (MG) and amyotrophic lateral sclerosis (ALS). Results: Identified subjects consisted of 11patients with MG and 11 patients with ALS. Multiple regression analysis revealed that only the difference of muscle influenced on DCR2 and DCR3, with no contribution from the different disorder (MG or ALS) or the initial amplitude of the compound muscle action potential (CMAP). Both DCR2 and DCR3 were significantly higher in deltoid than in APB. In ALS, the normalized CMAP amplitude was not different between APB and deltoid whereas the decremental percentage was significantly higher in deltoid, suggesting a lower safety factor of the neuromuscular transmission in proximal muscles. Conclusions: The decremental response completed more rapidly in deltoid than in APB which may be related to the lower safety factor also documented by this study. Significance: Unexpected early completion of the decrement such as at the second response in RNS is not a technical error but may be an extreme of the rapid completion in deltoid, a proximal muscle.

Non-traumatic Rectus Sheath Hematoma During Direct Oral Anticoagulation.

We report a case of anticoagulation therapy complicated by a non-traumatic rectus sheath hematoma (RSH). RSH is a relatively rare occurrence caused by bleeding into the rectus sheath following the rupture of the superior and inferior epigastric vessels combined with a primary tear of the rectus muscle fibers. Herein, we report a rare presentation of RSH in a 73-year-old man taking the direct oral anticoagulant (DOAC) apixaban orally. The patient presented with sudden right abdominal pain after a severe cough, which worsened with cough and movement. The Fothergill and Carnett signs were positive. The platelet count, renal function test, and the prothrombin time/international normalized ratio were within the normal range. The activated partial thromboplastin time was 40.0 s, slightly longer than normal. Computed tomography (CT) of the abdomen and pelvis showed RSH, and DOAC therapy was temporarily discontinued. Subsequently, RSH resolution was confirmed via CT four weeks after the onset. DOACs are safer and more efficacious than warfarin for patients with non-valvular atrial fibrillation. However, RSH is a potential complication of anticoagulant therapy. This case report demonstrates that RSH should be considered in the differential diagnosis of sudden-onset abdominal pain and mass in patients on DOACs.

Pathological features of glial cells and motor neurons in the anterior horn of the spinal cord in sporadic ALS using ADAR2 conditional knockout mice.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the selective degeneration of motor neurons (MNs). In the MNs of patients with ALS, adenosine deaminase acting on RNA 2 (ADAR2)-mediated RNA editing of GluA2 mRNA at the Q/R site is profoundly deficient. In genetically modified mice (ADAR2flox/flox/VAChT-Cre.Fast; AR2), the selective knockout of ADAR2 in cholinergic neurons induced progressive loss of lower MNs. MNs exhibiting an age-related increase in abnormal TDP-43 localization and reduced ADAR2 immunoreactivity are localized in the lateral areas of the anterior horns (AHs) in aged wild-type mice. However, the patterns in the AHs of AR2 mice remain unknown. In this study, we investigated whether similar degeneration is observed in AR2 mice. We compared the number of astrocytes and MNs in the lateral and medial AHs of the lumbar spinal cord of 12-month-old AR2 mice with age-matched wild-type mice. The number of MNs significantly decreased in both the lateral and medial areas in AR2 mice AHs, particularly in the former. The number of reactive astrocytes increased significantly in the lateral areas of the AHs of AR2 mice. In conclusion, stronger activation of astrocytes with reduction of MNs in the ADAR2 deficiency-related lateral area increases in AR2 mice AHs. Fast fatigable MNs are expected to be present in the lateral area of the AHs. We found that MN death is more common in the lateral area of AHs associated with FF MNs due to differences in vulnerability to MN under ADAR2 deficiency.