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BACKGROUND A strategy to predict mortality in elderly heart failure (HF) patients has not been established.Methods and Results:We retrospectively enrolled 413 HF patients aged ≥65 years (mean age 78 years) who had received comprehensive cardiac rehabilitation (CR) during hospitalization. Basic activities of daily life were assessed before discharge using the Barthel index (BI). Of 413 HF patients, 116 (28%) died during a median follow-up period of 1.90 years (interquartile range 1.20-3.23 years). An adjusted dose-dependent association analysis showed that the hazard ratio (HR) of mortality increased in an almost linear manner as the BI score decreased, and that a BI score of 85 corresponded to an HR of 1.0. Kaplan-Meier survival curves showed that the survival rate was lower for patients with a low BI (

Patients with left unilateral spatial neglect (USN) typically place the subjective midpoint to the right of the objective centre. Based on the previous findings (e.g., Ishiai et al. 1989, Brain, 112, 1485), we hypothesized that the patients with left USN may see the representational image of a line that extends equally towards either side of the subjective midpoint depending not upon the information about the leftward extent. The present study tested whether patients with left USN would place the subjective midpoint at the centre of their mental representation of the line. The participants were 10 patients with left USN and 10 neurologically healthy controls. We devised a new 'endpoint reproduction task' using a computer display with a touch panel to seek the representational image when patients with left USN bisect lines and asked the participants to reproduce the location of the right or left endpoint after bisecting lines. The results showed that the representational image of the bisected line depends primarily on the location of the objective right endpoint, not on the location of the objective left endpoint in space. The analyses of the estimated right and left representational extents confirmed our hypotheses that patients with left USN would bisect a line seeing the representational line image that centred across their subjective midpoint. We believe that the findings of the present study with the use of the endpoint reproduction task will contribute to a better understanding of the visuospatial process underlying line bisection of patients with left USN.

This study was aiming at investigating the extent of neuronal damage in cases of traumatic brain injury (TBI) with diffuse axonal injury (DAI) using 123I-iomazenil(IMZ) SPECT and MRI. We compared the findings in 31 patients with TBI without any major focal brain lesions and 25 age-matched normal controls. Subjects underwent 123I-IMZ SPECT and MRI, and also assessment by cognitive function tests. The partial volume effect of 123I-IMZ SPECT was corrected using MRI. In the patients with TBI, decreased spatial concentration of 123I-IMZ binding was detected in the medial frontal/orbitofrontal cortex, posterior cingulate gyrus, cuneus, precuneus, and superior region of the cerebellum. ROC analysis of 123I-IMZ SPECT for the detection of neuronal injury showed a high diagnostic ability of 123I-IMZ binding density for TBI in these areas. The decreased 123I-IMZ uptake density in the cuneus and precuneus was associated with cognitive decline after the injury. In the patients with TBI, brain atrophy was detected in the frontal lobe, anterior temporal and parietal cortex, corpus callosum, and posterior part of the cerebellum. Evaluation of the neuronal integrity by 123I-IMZ SPECT and MRI provides important information for the diagnosis and pathological interpretation in cases of TBI with DAI.

In this issue of the Journal of Neuropsychology, Abe and Ishiai (2022) report an experiment designed to probe the subjective experience of line bisection in neglect. A re-analysis of their data can also offer insights into how best to characterise neglect performance for this and other tasks. We show that sensitive measures of neglect can be obtained by quantifying the difference in the influence (or 'weighting') that each endpoint has on the response. The right endpoint is dramatically more influential than the left in people with neglect performing line bisection and endpoint reproduction tasks. This supports the view that neglect may limit the ability to simultaneously represent two locations, so that the response is determined primarily with respect to the right endpoint. We also discuss Abe and Ishiai's conclusion that bisection responses in neglect are accompanied by the subjective experience of a complete line extending equally to either side of the chosen midpoint.

Background Depression is a common symptom after stroke, but its neural substrates remain unclear. The ascending serotonergic system originates from the raphe nuclei in the brainstem. We hypothesized that depressive disorder due to brainstem infarction is associated with damage to the raphe nuclei. Methods We prospectively enrolled 19 patients who had the first-ever acute isolated brainstem infarction in an observational cross-sectional study. All patients were evaluated by using the Montgomery Asberg Depression Rating Scale (MADRS), the clinician-rated version of Apathy Evaluation Scale (AES-C) and Mini-Mental State Examination (MMSE). Depressive disorder was diagnosed according to DSM-5 and MADRS score of 12 or greater. Diffusion tensor imaging and proton density-weighted images were used to identify damage in the raphe nuclei. Accordingly, patients were classified into either the raphe-nuclei–damaged or intact group. Prevalence of depressive disorder and the MADRS, AES-C, and MMSE scores were compared between the two groups. Results Depressive disorder was more frequent in the damaged group (n=6) than in the intact group (n=13) (83% vs. 15%; P=0.01). MADRS scores were higher in the damaged group than in the intact group (mean±1 SD, 17.5±7.9 vs. 7.0±4.4; P=0.002), whereas the AES-C and MMSE scores did not differ between groups. Limitations We did not assess the damage to the ascending projection fibers from the raphe nuclei. Conclusions Our results suggest that damage to the raphe nuclei underlies depressive disorder due to brainstem infarction, possibly via serotonergic denervation.

We reported a male who showed typing disorders after resection of a tumor in the left posterior superior and middle frontal gyri. He was a right-handed Japanese in his 50s and was good at touch typing as a system engineer. After the tumor resection, he presented typing errors and slightly impaired dexterity of his right fingers. The results of neuropsychological examinations indicated that his typing impairment was not due to aphasia or agraphia of kana letters (Japanese syllabogram). Typing errors were classified into adjacent key, non-adjacent key, omission, and insertion errors. Adjacent key, omission, and insertion errors were commonly found in both words and non-words. Adjacent key errors appeared more frequently in the right hand than the left-hand assigned keys, which may be explained by impaired dexterity of the right fingers associated with the left frontal lesion. Non-adjacent key errors were found exclusively for words and more frequently with the left hand than with the right hand. We consider that the patient's left frontal lesion may have impaired the motor engrams of word typing or its output process necessary to type individual words as a programmed series of pushing keys. (Received November 2, 2018; Accepted July 16, 2019; Published October 1, 2019).

Background Although spinal cord injury (SCI) is a major cause of disability, current therapeutic options remain limited. Recent progress in cellular therapy with mesenchymal stem cells (MSCs) has provided improved function in animal models of SCI. We investigated the safety and feasibility of intravenous infusion of MSCs for SCI patients and assessed functional status after MSC infusion. Methods In this phase 2 study of intravenous infusion of autologous MSCs cultured in auto-serum, a single infusion of MSCs under Good Manufacturing Practice (GMP) production was delivered in 13 SCI patients. In addition to assessing feasibility and safety, neurological function was assessed using the American Spinal Injury Association Impairment Scale (ASIA), International Standards for Neurological and Functional Classification of Spinal Cord (ISCSCI-92). Ability of daily living was assessed using Spinal Cord Independence Measure (SCIM-III). The study protocol was based on advice provided by the Pharmaceuticals and Medical Devices Agency in Japan. The trial was registered with the Japan Medical Association (JMA-IIA00154). Results No serious adverse events were associated with MSC injection. There was neurologic improvement based on ASIA grade in 12 of the 13 patients at six months post-MSC infusion. Five of six patients classified as ASIA A prior to MSC infusion improved to ASIA B (3/6) or ASIA C (2/6), two ASIA B patients improved to ASIA C (1/2) or ASIA D (1/2), five ASIA C patients improved and reached a functional status of ASIA D (5/5). Notably, improvement from ASIA C to ASIA D was observed one day following MSC infusion for all five patients. Assessment of both ISCSCI-92, SCIM-III also demonstrated functional improvements at six months after MSC infusion, compared to the scores prior to MSC infusion in all patients. Conclusion While we emphasize that this study was unblinded, and does not exclude placebo effects or a contribution of endogenous recovery or observer bias, our observations provide evidence supporting the feasibility, safety and functional improvements of infused MSCs into patients with SCI.

[Purpose] The aim of this study was to determine which factors, including pulmonary, physical, and mental functions; dyspnea; and daily physical activity (PA) affect the 6-minute walk distance (6MWD) in IPF patients. [Subjects and Methods] The pulmonary, physical, and mental functions; dyspnea; PA; and 6MWD were assessed in 38 outpatients with IPF. PA was represented by the mean number of steps per day. [Results] The mean 6MWD was 443.8 m (SD, 98.5), and the mean number of steps per day showing PA was 5148.4 (SD, 3295.7). The 6MWD was correlated with age, base dyspnea index, vital capacity (VC), diffusion capacity of carbon monoxide, quadriceps force (QF), dyspnea during the 6-minute walk test, and PA. Stepwise multiple regression analysis revealed that VC (β=0.382), QF (β=0.272), and PA (β=0.574) were contributing factors of the 6MWD. [Conclusion] In patients with IPF, PA has a greater effect on the 6MWD than VC and QF. The evaluation of daily PA, in addition to physiological and muscle functions, is important in patients with IPF.

Background Whether the short-term effect of cardiac rehabilitation (CR) in elderly patients with heart failure (HF) is influenced by nutritional status is uncertain, so the present study investigated the effect of nutritional status on functional recovery after CR in elderly HF inpatients.Methods and Results:We enrolled 145 patients admitted for treatment of HF who were aged ≥65 years and had a low functional status defined as a Barthel index (BI) score ≤85 points at the commencement of CR. Nutritional status was assessed by the Mini Nutritional Assessment Short Form (MNA-SF) and total energy intake per day. The primary endpoint was functional status determined by the BI score at discharge. The median CR period was 20 days (interquartile range: 14-34 days), and 87 patients (60%) were functionally dependent (BI score ≤85) at discharge. Multivariate logistic regression analysis showed that MNA-SF score (odds ratio [OR]: 0.76, P=0.02) and total energy intake at the commencement of CR (OR: 0.91, P=0.02) were independent predictors of functional dependence after CR. MNA-SF score ≤7 and total energy intake ≤24.5 kcal/kg/day predicted functional dependence at discharge with moderate sensitivity and specificity. Conclusions MNA-SF score and total energy intake at the commencement of CR are novel predictors of the extent of functional recovery of elderly HF inpatients after in-hospital CR.

[Purpose] The current study aimed to investigate factors affecting dyspnea after the 6-minute walk test (6MWT) in idiopathic pulmonary fibrosis (IPF) patients presenting with hypoxemia. [Subjects and Methods] The subjects were IPF out-patients with stable symptoms whose percutaneous arterial oxygen saturation fell to 88% during the 6MWT test. Quadriceps force, 6-minute walk distance (6MWD), dyspnea after the 6MWT, and leg fatigue (LF) were evaluated as exercise-related variables. [Results] The subjects were 14 patients (mean age 73.6 ± 6.3 years) classed based on the modified Medical Research Council dyspnea scale as 0 for 2 patients, 1 for 6 patients, and 2 for 6 patients, indicating that the patients were comparatively mild cases. Mean 6MWD was 408.9 ± 102.4 m, and dyspnea after the 6MWT and LF were 3.0 ± 1.4 and 1.5 ± 1.5, respectively. Dyspnea after the 6MWT was correlated with vital capacity (VC), forced vital capacity, and LF. Stepwise multiple regression analysis identified VC and LF as factors significantly affecting dyspnea after the 6MWT. [Conclusion] The results of this study demonstrated that it is necessary to evaluate both pulmonary function and LF in IPF patients presenting with exercise-induced hypoxemia and exertional dyspnea.

Objective The basal temporal language area (BTLA) is considered to have several functions in language processing; however, its brain network is still unknown. This study investigated the distribution and networks of the BTLA using a combination of electric cortical stimulation and diffusion tensor imaging (DTI). Method 10 patients with intractable focal epilepsy who underwent presurgical evaluation with subdural electrodes were enrolled in this study (language dominant side: 6 patients, language nondominant side: 4 patients). Electric stimulation at 50 Hz was applied to the electrodes during Japanese sentence reading, morphograms (kanji) reading, and syllabograms (kana) reading tasks to identify the BTLA. DTI was used to identify the subcortical fibers originating from the BTLA found by electric stimulation. Results The BTLA was found in 6 patients who underwent implantation of the subdural electrodes in the dominant hemisphere. The BTLA was located anywhere between 20 mm and 56 mm posterior to the temporal tips. In 3 patients, electric stimulation of some or all areas within the BTLA induced disturbance in reading of kanji words only. DTI detected the inferior longitudinal fasciculus (ILF) in all patients and the uncinate fasciculus (UF) in 1 patient, originating from the BTLA. ILF was detected from both kanji-specific areas and kanji-nonspecific areas. Conclusion This study indicates that the network of the BTLA is a part of a ventral stream and is mainly composed of the ILF, which acts as a critical structure for lexical retrieval. ILF is also associated with the specific processing of kanji words.

Left hemispatial neglect (neglect) is an impaired state of spatial attention. We aimed to reconstruct structural connectivity in the spatial attention network and to identify disconnection patterns underlying neglect. We enrolled 59 right-handed patients who had their first-ever infarction in the right hemisphere and classified them into neglect group (34 patients with neglect) and control group (25 patients without neglect). The neglect group was further subcategorized into 6 subgroups based on infarcted vascular territories. Diffusion tensor imaging data were obtained from all patients. Fractional anisotropy maps were compared between neglect group/subgroups and the control group by using non-parametric voxel-based analysis, generating a lesion path mask. Probabilistic tractography analysis using the lesion path mask reconstructed the following structural connectivity in the spatial attention network, which is specifically damaged in neglect patients: (1) superior longitudinal fasciculus (SLF) I connecting the superior parietal lobule/intraparietal sulcus with the superior frontal gyrus/frontal eye field (SFG/FEF) (dorsal attention network); (2) SLF III/the arcuate fasciculus (AF) and the extreme capsule/inferior fronto-occipital fasciculus (IFOF) connecting the right inferior parietal lobule/temporoparietal junction/superior temporal gyrus (IPL/TPJ/STG) with the middle frontal gyrus/inferior frontal gyrus (ventral attention network); (3) the thalamic radiations to the spatial attention-related cortices; and (4) SLF II and IFOF interconnecting dorsal and ventral attention networks. Individual analysis indicated that isolated damage in SLF I, SLF II, SLF III/AF or the thalamic radiations to IPL/TPJ/STG due to posterior cerebral artery infarction, or simultaneous damage in four thalamic radiations due to anterior choroidal artery infarction, underlies different phenotypes of neglect.

The neural basis of language had been considered as a simple model consisting of the Broca's area, the Wernicke's area, and the arcuate fasciculus (AF) connecting the above two cortical areas. However, it has grown to a larger and more complex model based upon recent advancements in neuroscience such as precise imaging studies of aphasic patients, diffusion tensor imaging studies, functional magnetic resonance imaging studies, and electrophysiological studies with cortical and subcortical stimulation during awake surgery. In the present model, language is considered to be processed through two distinct pathways, the dorsal stream and the ventral stream. The core of the dorsal stream is the superior longitudinal fasciculus/AF, which is mainly associated with phonological processing. On the other hand, semantic processing is done mainly with the ventral stream consisting of the inferior fronto-occipital fasciculus and the intratemporal networks. The frontal aslant tract has recently been named the deep frontal tract connecting the supplementary motor area and the Broca's area and it plays an important role in driving and initiating speech. It is necessary for every neurosurgeon to have basic knowledge of the neural basis of language. This knowledge is essential to plan safer surgery and preserve the above neural structures during surgery.

ヒマワリのような花の左側の花びらがなければそれに気づき，左半分が塀か何かに遮られていれば隠れて見えないと感じる。右半球の脳卒中後に左半側空間無視が生じた患者は，花の絵を右半分しか模写しなくても，手本と同じように描けたと言い，左側の描き落としに気づかない。もちろん，手本の花の絵について右半分の絵であるとか，右半分しか見えないとか言うことはない。半側空間無視患者の注意は右方へ向きやすく，左方へ向きにくい。少なくとも花の絵くらいの大きさの対象において，健常人では左右への注意のバランスに極端な差が生じることはない。ところが，半側空間無視患者では，花の絵に注目した時，左右に急峻な注意の勾配が生じている。注意が向かない空間は意識に上らず，喪失感も生じない。一方で，注意の向いた右側部分の情報によって，対象が何であるかの認知は成立する。このような，空間の認知と対象の認知のギャップを考えながら，半側空間無視の視覚世界を理解する試みを展開したい。

半側空間無視は，空間性注意の右方偏倚を基本とし，課題に対する性急さ，用いる方略の不適切さなど，非空間性要因が加わった最終的表現形である。非空間性要因は，課題ごとに指示を工夫すると改善できる場合がある。注意の右方偏倚の矯正目的で「左を見て」と指示する際は，空間的フレームの明確な左側を示すと有効である。しかし，フレーム内の処理向上には，探索の跳躍を抑えるpacing を要する。保存された感覚を一側性に刺激する方法には，カロリック刺激，視運動性刺激，頸部筋振動刺激があり，刺激中の無視改善効果がある。プリズム順応は短時間で感覚—運動協調に変容を創り出し，持続性の無視改善効果が期待されている。しかし，効果は症例と課題によって異なり，今後の検討を要する。新旧の方法を交えて多角的にアプローチし，半側空間無視患者の日常生活活動向上を目指したい。

This study evaluates the accuracy of goniometric measurement of fixated proximal interphalangeal (PIP) joints using fresh cadavers. Sixteen fingers in four right hands were evaluated. Angles of PIP joints obtained by three examiners, two methods (lateral, dorsal), three goniometers (plastic A, B, and a metal model), and four different fingers were compared for the accuracy of measurement. The difference of angles obtained from goniometric measurement and x-ray films of cadaver fingers was defined as "angle discrepancy." Analysis of interrater reliability proved that there was a high correlation coefficient between examiners. With the lateral method, no statistically significant difference in angle discrepancy between goniometers was observed. On the other hand, with the dorsal method, the angle discrepancy of plastic A was statistically significantly greater than plastic B in the results of two examiners (p

Background Intravenous infusion of mesenchymal stem cells (MSCs) derived from adult bone marrow improves behavioral function in rat stroke models. Rehabilitation therapy through physical exercise also provides therapeutic efficacy for cerebral ischemia. Objective The purpose of this study was to investigate whether synergic effects of daily rehabilitation and intravenous infusion of MSCs has therapeutic effects after stroke in rats. Design This was an experimental study. Methods A permanent middle cerebral artery occlusion (MCAO) was induced by intraluminal vascular occlusion with a microfilament. Four experimental groups were studied: group 1 (vehicle only, n=10), group 2 (vehicle + exercise, n=10), group 3 (MSCs only, n=10), and group 4 (MSCs + exercise, n=10). Rat MSCs were intravenously infused at 6 hours after MCAO, and the rats received daily rehabilitation with treadmill running exercise for 20 minutes. Lesion size was assessed at 1, 14, and 35 days using magnetic resonance imaging. Functional outcome was assessed using the Limb Placement Test. Results Both combined therapy and MSC infusion reduced lesion volume, induced synaptogenesis, and elicited functional improvement compared with the groups without MSC infusion, but the effect was greater in the combined therapy group. Limitations A limitation of this study is that the results were limited to an animal model and cannot be generalized to humans. Conclusions The data indicate that the combined therapy of daily rehabilitation and intravenous infusion of MSCs improved functional outcome in a rat MCAO model.

Patients with left unilateral spatial neglect following right hemisphere lesions usually err rightward when bisecting a horizontal line. For very short lines (e.g. 25 mm), however, leftward errors or seemingly 'right' neglect is often observed. To explain this paradox of crossover in the direction of errors, rather complicated models have been introduced as to the distribution of attention. Neglect may be hypothesized to occur in representational process of a line or estimation of the midpoint on the formed image, or both. We devised a line image task using a computer display with a touch panel and approached the representational image of a line to be bisected. Three patients with typical left neglect were presented with a line and forced to see its whole extent with cueing to the left endpoint. After disappearance of the line, they pointed to the right endpoint, the left endpoint, or the subjective midpoint according to their representational image. The line image between the reproduced right and left endpoints was appropriately formed for the 200 mm lines. However, the images for the shorter 25 and 100 mm lines were longer than the physical lengths with overextension to the left side. These results proved the context effect that short lines may be perceived longer when they are presented in combination with longer lines. One of our patients had an extensive lesion that involved the frontal, temporal, and parietal lobes, and the other two had a lesion restricted to the posterior right hemisphere. The image for a fully perceived line may be represented far enough into left space even when left neglect occurs after a lesion that involves the right parietal lobe. The patients with neglect placed the subjective midpoint rightward from the centre of the stimulus line for the 100 and 200 mm lines and leftward for the 25 mm lines. This crossover of bisection errors disappeared when the displacement of the subjective midpoint was measured from the centre of the representational line image. Left neglect may occur consistently in estimation of the subjective midpoint on the representational image, which may be explained by a simple rightward bias of attentional distribution.

Objectives—To clarify the mechanisms of left unilateral spatial neglect found in the bisection of lines after cueing to the left end point and to determine whether neglect occurs for the mental representation of a line. Methods—A new representational bisection task was developed to eliminate the influence of the right segment of the physical line that would attract attention. Eight patients with typical left unilateral spatial neglect underwent line and representational bisection tasks on a computer display with a touch panel. In the line bisection with cueing, they bisected a line after touching the left end point. In the representational bisection, the patients were presented with a line until they touched the left end point. On the blank display, they pointed to the subjective midpoint of the erased line. The performances of the two bisection tasks were compared when the length and position of stimulus lines were varied. Results—The rightward errors in the representational bisection were greater than or equivalent to those in the line bisection with cueing. The eVect of line length in which the errors became greater for the longer lines was equally found in the line bisection with cueing and the representational bisection.This was confirmed in the condition where the right end point was placed at a fixed position and the line length was varied. Conclusions—After cueing to the left end point, rightward bisection errors of patients with neglect are not caused by overattention to the right segment of the physical line. Left neglect occurs mainly for the mental representation formed at the time of cueing or seeing the whole extent of a line. (J Neurol Neurosurg Psychiatry 2000;69:745‐750)

Cube-copying is often used to assess constructional ability of brain-damaged patients and the influence of unilateral spatial neglect is often pointed out in patients with right hemisphere lesions. However, some patients with severe neglect perform cube-copying satisfactorily. The aim of the present study is to identify the factors that affect the performance of cube-copying in patients with left unilateral spatial neglect. Constructional performance was investigated in 100 patients with unilateral spatial neglect using a task to copy the Necker cube. The relationship of the patients' cube-copying performance to the severity of their neglect, as well as other factors (verbal intelligence, age, duration after onset of the disease, educational level, lesion site, piecemeal approach, and side of starting to copy) was analyzed. Twenty-two normal subjects also participated in this study as controls. Among many factors adopted for analysis, neglect severity and verbal intelligence were found to be primary factors affecting the cube-copying performance of the patients with unilateral spatial neglect. The effect of neglect severity on cube-copying performance was apparent in the patients whose verbal intelligence was deteriorated, but was not observed in the patients with preserved verbal intelligence. Similarly, the effect of verbal intelligence on cube-copying performance was apparent in the patients with severe neglect, but not in the patients with mild neglect. We conclude that constructional ability in the copying of a cube is determined by verbal intelligence, as well as by the severity of unilateral spatial neglect.

The difficulty that patients with unilateral spatial neglect (USN) have in exploring into the contralesional space may be explained by motor or attentional disorder. We experienced a patient with severe USN following cerebral infarction in the right postrolandic region, who showed a strong resistance to leftward movement. We devised two sets of tasks using a whiteboard. In the first experiment, the patient showed great difficulty in tracing a line from the right endpoint to the left endpoint. The examiner barely made him start further tracing even by pushing the hand leftward. By contrast, he quickly erased a whole line leftward with an eraser pen. In the second experiment, he was required to erase a line with or without an attention-attracting stimulus at the right endpoint. Not only the leftward extent, but also the velocity of erasing, were decreased when there was a stimulus at the right endpoint. The results of the two experiments suggest that the ability of leftward movement itself was pres...

Patients with relatively mild unilateral spatial neglect underwent the line bisection task with self-estimation, where they were asked two different questions about the relationship of their subjective midpoint to the line. For the first trial, all patients responded by yes when asked whether their subjective midpoint was placed at the center of the line, but by left or right when asked to indicate the longer segment of the bisected line. In the subsequent trials, they repeatedly reported that their subjective midpoints were placed at the true center, even after they had recognized their bisection errors when indicating the longer segment. Of the 32 patients, 28 kept on showing this pattern of responses in almost all the 30 trials. Moreover, the patients who could estimate the longer segment showed no improvement of line bisection throughout the trials. Their performances strongly depended upon the task demand regarding the subjective midpoint. These results demonstrate that the patients treated the two related tasks as independent. Accordingly, they could not improve their performances on one task with the feedback from their performances on the other. The lack of association between the responses to two related task demands may be one of the factors that prevent patients with unilateral spatial neglect from improving the deficit.

Three patients with unilateral spatial neglect could detect the difference of length between the right and left segments when a line had a transection mark. To examine the effect of response mode, the manual line bisection task and a new “line bisection task by fixation” were given to the patients. In tasks that used lines with no landmark, they showed apparent rightward errors. The results suggest that line bisection is not a task that examines the ability of patients with neglect to compare the right and left extents of a line. Where to fixate as the subjective midpoint may determine the rightward errors of bisection, whether manual response is used or not.

We examined the effect of line length and viewing distance on the line bisection performance in near space in five patients with left unilateral spatial neglect following right parietal lesions. A line bisection task by fixation was devised to avoid the influence of manual responses. The rightward deviation measured in visual angle increased linearly as a function of the visual angle of lines 150 mm or more long. This linearity, however, did not hold for lines of 100 mm or less. The deviation measured in length was nearly constant for each of these short lengths, even when the visual angle was varied at different viewing distances. The patients therefore discriminated the objective lengths of the short lines. For small objects, neglect patients may distribute attention mainly on the coordinates scaled for objective size.

We participated as physiatrists in Honmou et al's study that designed to assess feasibility and safety of transplantation of autologous human mesenchymal stem cells in patients with cerebral infarction, and tried to detect improvements that were distinguishable from usual course of rehabilitation. Improvements of motor function were found in rather small functional units, such as movements in one of the fingers, toes, and a single joint of an extremity. In the methods of evaluation, Brunnstrom stage may detect gross changes, while the more detailed scales were necessary for assessment of recovery after transplantation of stem cells. In the investigator-initiated clinical trial of stem cell therapy for stroke, we are going to include fine-grained evaluation methods and investigate the most suitable technique of rehabilitation for patients after treatment.

The present study examined 13 patients with typical left unilateral spatial neglect to explore the mechanisms of neglect in copying a single object. All patients identified the figure of a sunflower as a flower that had petals all around the central circle. Besides, in the free viewing of the flowers prepared by the examiner, 10 of the 13 patients could discriminate between the presence and absence of the left-sided petals. When copying the flower, however, they always left the left side unfinished without noticing the incompleteness. Whether perception in the left visual field was impaired or not was irrelevant to the performances in the copying and the free viewing of the flowers. We consider the mechanism of left unilateral spatial neglect in copying a flower as follows. Small leftward shift of attention may take place during the free observation of the stimulus flower. While copying, however, neglect patients pay attention exclusively to the right-sided petals they are drawing. The strong engagement of attention to the right side results in the lack of discovery of the left-sided omission. The close integration of attentional and premotor mechanisms seems to be crucial for the appearance of unilateral spatial neglect in copying a single object. Copyright © 1996 Elsevier Science Ltd

We reported a dramatic phenomenon of appearance and disappearance of left unilateral spatial neglect for the same single object. In experiment 1, four patients with mild neglect who copied a single flower satisfactorily showed left neglect in copying of the same flower when it was accompanied with some peripheral stimuli. In experiment 2, we included three additional conditions to determine the stimulus component crucial for left neglect of the flower: a flower with a stem and a flower with either right or left peripheral stimuli were also used for copying. Overall results showed that neglect was most evident for the flower with the right peripheral stimuli. On the other hand, the presence of left stimuli provoked less severe neglect of the flower, which was as mild as that in the single flower condition. The results were explained in terms of an attentional mechanism underlying unilateral spatial neglect. When copying the flower with peripheral stimuli on both sides or on the right side, the stimuli on the right side might attract the patient's attention. Consequently, he exhibited left neglect on the central flower. On the other hand, neglect was less evident in the other conditions, since the figures did not include such attention-attracting stimuli on the right side.

We examined the eye-fixation pattern of a patient with severe left unilateral spatial neglect who showed leftward searches of various extent in more than half of line bisection trials. Because of complete left homonymous hemianopia, he perceived only the segment of the line between its right endpoint and the point of the leftmost fixation. In the trials with leftward searches, he frequently placed the subjective midpoint on the right part of the perceived segment. In the trials without leftward searches, he placed it near the left extreme point of the perceived segment. For all these bisections, the subjective midpoint was constantly placed far to the right of the true midpoint of the line irrespective of the length perceived. We consider that in severe left unilateral spatial neglect, rightward attentional bias is the predominant factor that determines where to place the subjective midpoint. Transient attentional shift to the left may produce leftward searches, but it does not induce effective processing of line bisection.

慢性期まで続いた半側空間無視の改善について，比較的長期間観察しえた症例群を対象として，代償と回復の側面から検討した。無視の回復としては，左方探索の出現と病識の獲得が重要である。左方探索の出現により，抹消試験のような探索課題は改善するが，多くの場合，注意の右方偏位が残っており，線分二等分試験や花の絵の模写など，単一対象の左側に無視が見られることが多い。また，刺激密度の高い日常生活場面でも無視が見られる。病識の出現に伴い，左側の対象を健側に移して処理したり，指摘された誤反応に対する修正を行うといった代償反応も見られるようになる。一方，言語性知識による代償は，病識出現前に見られることもある。半側空間無視は，慢性期に入ってからでも徐々に改善することが多く，また，代償反応による日常生活への適応も起こることから，６ヵ月以上にわたる長期リハビリテーションを考慮してもよい場合が少なくない。

We analysed the performances of 69 patients with left unilateral spatial neglect in copying a multi-object figure, as well as their performance of the line cancellation and line bisection tests. Three patterns of copying were mainly observed. The first pattern was almost satisfactory performance in copying the central figure with occasional omission of the elements located more laterally to the left. The second pattern was omission of the left half of the whole figure, which was the pattern expected of patients with typical left unilateral spatial neglect. The third pattern was left unilateral spatial neglect when copying the central figure, with favourable copying of left lateral objects; this may be regarded as "object-centered" neglect. Performance of the line cancellation test, which requires exploratory ability, was significantly better for the patients with the third pattern than for those with the second pattern. A significant difference was also observed between the two groups of patients in performance of the line bisection test, in which exploratory ability plays a more minor role. No significant difference was found in performance of the line cancellation and line bisection tests between the patients with the third and first patterns, in spite of remarkable differences in their copying performances. No distinctive characteristics were found for any group of patients as regards lesion, age, duration after onset, education, and WAIS scores. Therefore we concluded that in most of our patients with neglect, these diverse patterns of copying deficits resulted from different levels of neglect severity but not from different types of unilateral spatial neglect.

Three patients with left unilateral spatial neglect after predominantly frontal lobe lesions were asked to extend a horizontal line leftwards to double its original length. In this line extension task, they readily executed movements in or towards the contralesional left space. They performed the task in the left and right hemispaces as well as in the midline. The mean extension lengths did not differ significantly among these three spatial conditions. These results suggest that directional hypokinesia takes little part in left unilateral spatial neglect due to frontal lobe lesions. It is considered that the patients could execute leftward movements as the task oriented their attention sufficiently to the left. Two of the three patients, like reported cases with frontal neglect, showed a typical exploratory deficit for the left space in the line cancellation test. Such a deficit found in the traditional tasks, however, does not mean the presence of directional hypokinesia. All three patients showed visual extinction on double simultaneous stimulation. An attentional mechanism seems to play a predominant part in unilateral spatial neglect due to frontal lesions.

“Unilateral spatial neglect” or “hemispatial neglect” is a commonly used term for expressing the failure of brain damaged patients to attend to and explore stimuli presented in the space contralateral to their lesion (Heilman, Bowers, Valenstein, & Watson, 1987). Because unilateral spatial neglect is observed under conditions where movements of the eyes and head are permitted, trunk-hemispace, determined by the sagittal midplane of the body, is treated as the most important conceptual space for neglect (Heilman et al., 1987). However, the neglected space is not the unilateral half of space or hemispace. It is more accurate to state that there is a gradient in spatial locations subject to neglect: In left unilateral spatial neglect, the more a stimulus is located to the left, the more frequently it is neglected (Kinsbourne, 1987). There is no constant boundary between the neglected and non-neglected spaces for individual patients. We found that neglect patients could explore more to the left in th...

A nontraumatic spinal cord injury related to surfing is called surfer's myelopathy. The case of a 26-yr-old man who became paraplegic after surfing without apparent traumatic events is described. Physical examination revealed a spinal cord injury at T12 according to the American Spinal Injury Association Impairment Scale A. The initial magnetic resonance image revealed a fusiform swelling of the spinal cord from T7-8 to the conus, which was hyperintense on T2-weighted images. After 6 mos of rehabilitation, the patient was followed for more than 1 yr after onset. He became able to walk with knee-ankle-foot-orthoses without assistance. A magnetic resonance image obtained 1 yr after the onset of paraplegia showed an atrophic spinal cord from T7-8 to the conus. The course of the neurologic findings and the imaging studies suggest that the pathogenesis of surfer's myelopathy may be ischemia of the anterior spinal artery territory induced by the abnormal trunk posture while surfing.

Transplantation of human mesenchymal stem cells has been shown to reduce infarct size and improve functional outcome in animal models of stroke. Here, we report a study designed to assess feasibility and safety of transplantation of autologous human mesenchymal stem cells expanded in autologous human serum in stroke patients. We report an unblinded study on 12 patients with ischaemic grey matter, white matter and mixed lesions, in contrast to a prior study on autologous mesenchymal stem cells expanded in foetal calf serum that focused on grey matter lesions. Cells cultured in human serum expanded more rapidly than in foetal calf serum, reducing cell preparation time and risk of transmissible disorders such as bovine spongiform encephalomyelitis. Autologous mesenchymal stem cells were delivered intravenously 36-133 days post-stroke. All patients had magnetic resonance angiography to identify vascular lesions, and magnetic resonance imaging prior to cell infusion and at intervals up to 1 year after. Magnetic resonance perfusion-imaging and 3D-tractography were carried out in some patients. Neurological status was scored using the National Institutes of Health Stroke Scale and modified Rankin scores. We did not observe any central nervous system tumours, abnormal cell growths or neurological deterioration, and there was no evidence for venous thromboembolism, systemic malignancy or systemic infection in any of the patients following stem cell infusion. The median daily rate of National Institutes of Health Stroke Scale change was 0.36 during the first week post-infusion, compared with a median daily rate of change of 0.04 from the first day of testing to immediately before infusion. Daily rates of change in National Institutes of Health Stroke Scale scores during longer post-infusion intervals that more closely matched the interval between initial scoring and cell infusion also showed an increase following cell infusion. Mean lesion volume as assessed by magnetic resonance imaging was reduced by >20% at 1 week post-cell infusion. While we would emphasize that the current study was unblinded, did not assess overall function or relative functional importance of different types of deficits, and does not exclude placebo effects or a contribution of recovery as a result of the natural history of stroke, our observations provide evidence supporting the feasibility and safety of delivery of a relatively large dose of autologous mesenchymal human stem cells, cultured in autologous human serum, into human subjects with stroke and support the need for additional blinded, placebo-controlled studies on autologous mesenchymal human stem cell infusion in stroke.

Insulin-like growth factor I (IGF-I) is expressed in many tissues, including bone, and acts on the proliferation and differentiation of osteoblasts as an autocrine/paracrine regulator. Tight-junction proteins have been detected in osteoblasts, and direct cell-to-cell interactions may modulate osteoblast function with respect, for example, to gap junctions. In order to investigate the regulation of expression of tight-junction molecules and of function during bone differentiation, osteoblast-like MC3T3-E1 cells and osteocyte-like MLO-Y4 cells were treated with IGF-I. In both MC3T3-E1 cells and MLO-Y4 cells, the tight-junction molecules occludin, claudin-1, -2, and -6, and the gap-junction molecule connexin 43 (Cx43) were detected by reverse transcription with polymerase chain reaction. In MC3T3-E1 cells but not MLO-Y4 cells, mRNAs of claudin-1, -2, and -6, Cx43, and type I collagen, and proteins of claudin-1 and Cx43 were increased after treatment with IGF-I. Such treatment significantly decreased paracellular permeability in MC3T3-E1 cells. The expression of claudin-1 in MC3T3-E1 cells after IGF-I treatment was mainly upregulated via a mitogen-activated protein (MAP)-kinase pathway and, in part, modulated by a PI3-kinase pathway, whereas Cx43 expression and the mediated gap-junctional intercellular communication protein did not contribute to the upregulation. Furthermore, in MC3T3-E1 cells during wound healing, upregulation of claudin-1 was observed together with an increase of IGF-I and type I collagen. These findings suggest that the induction of tight-junction protein claudin-1 and paracellular permeability during the differentiation of osteoblast-like MC3T3-E1 cells after treatment with IGF-I is regulated via a MAP-kinase pathway, but not with respect to gap junctions.

側頭葉後下部の出血性脳梗塞により，漢字の失書をきたした症例を対象とし，書取り不可能な漢字の視覚認知と書字動作に障害がないかを明らかにするため，写字過程の詳細な分析を行った。書取り可能な漢字と不可能な漢字から，字画数が一致するように選んだ28字の写字過程をアイカメラで記録した。手本の平均注視時間と平均注視回数は，書取り可能な漢字と不可能な漢字の間で差がなかった。また，平均書字時間も差がなく，写字過程における筆順の誤りは，書取り可能・不可能な漢字とも１文字ずつであった。以上より，書取り不可能な漢字であっても，手本を見て書くべき漢字がわかった場合には，ただちに自分の字体で正しく書き下すことができることが明らかとなった。このことは字画数が多いほど，また，習得学年が高いほど漢字の失書が重度となる点とともに，側頭葉後下部損傷による漢字の失書が，漢字の想起障害による可能性を示唆するものと考えられた。

The purpose of this study was to assess the relationship between the positioning of upper extremity and gliding distance of the median nerve during passive and active motion of the wrist and fingers. The longitudinal gliding of the medial nerve in the forearm was measured in 34 healthy subjects by ultrasonographic dynamic images. Those images were analyzed in a cross-correlation algorithm advocated by Dilley et al. (2001). In this experiment, passive extension of the wrist and fingers was applied manually by an examiner in four positions (elbow flexion and extension with forearm pronation, and elbow flexion and extension with forearm supination), two types of active finger motions (Hook and Grasp) were performed by the subjects. The distally oriented median nerve gliding ranged from 1.9 (in elbow extension with forearm pronation) to 3.0 mm (in elbow flexion with forearm supination) during passive extension of the wrist and fingers. There was a statistically significant difference in nerve gliding between the positions (p = 0.001). During active digital movement, the proximally oriented nerve gliding was observed from 0.8 (in the hook) to 1.3 mm (in the grasp). There was a significant difference in nerve gliding between the two ways of active finger motions (p = 0.001). On the basis of the data obtained from this study, it is concluded that forearm supination is the preferred position for the passive median nerve gliding exercise because of large distally oriented nerve gliding. The active digital motion with full finger grip may be an effective procedure to produce proximally oriented median nerve gliding.

Eye-fixation patterns, which include ocular searching and fixation, may change with tasks, stimuli, and instructions. This article reviews our studies over 18 years on eye-fixation patterns of neglect patients and aims to elucidate the visuospatial processing of unilateral spatial neglect.We recorded eye-fixation patterns when patients with neglect bisected a line in various conditions.Patients with neglect rarely searched to the left side when bisecting a line of the ordinary length (e.g., 200 mm). They persisted in fixating a right-side point, at which they later marked the subjective midpoint. They made no effective comparison between the leftward and rightward extents not only for a whole line but also for its explored right segment. Where they 'favored' to fixate as the subjective midpoint depended strongly upon the location of the right endpoint in space. Their representational image of a line was also estimated with modified line bisection tasks performed on a touch-panel display.For patients with neglect, the representational image of a line may be formed on the basis of the attended segment between the right endpoint and the favored point of fixation. The line bisection task, if combined with recording of eye-fixation, would further contribute to elucidation of the mechanisms underlying neglect.