Abnormalities in skilled reaching movements are improved by peripheral anesthetization of the less-affected forelimb after sensorimotor cortical infarcts in rats

Unilateral damage to sensorimotor cortical (SMC) regions can profoundly impair skilled reaching function in the contralesional forelimb. Such damage also results in impairments and compensatory changes in the less-affected/ipsilesional forelimb, but these effects remain poorly understood. Furthermore, anesthetization of the ipsilesional hand in humans with cerebral infarcts has been reported to produce transient functional improvements in the paretic hand [Floel A, Nagorsen U, Werhahn KJ, Ravindran S, Birbaumer N, Knecht S, et al. Influence of somatosensory input on motor function in patients with chronic stroke. Ann Neurol 2004;56:206-12; Voller B, Floel A, Werhahn KJ, Ravindran S, Wu CW, Cohen LG. Contralateral hand anesthesia transiently improves poststroke sensory deficits. Ann Neurol 2006;59:385-8]. One aim of this study was to sensitively assay the bilateral effects of unilateral ischemic SMC damage on performance of a unimanual skilled reaching task (the single pellet retrieval task) that rats had acquired pre-operatively with each forelimb. The second aim was to determine whether partially recovered contralesional reaching function is influenced by anesthetization of the ipsilesional forelimb. Unilateral SMC lesions were found to result in transient ipsilesional impairments in reaching success and significant ipsilesional abnormalities in reaching movements compared with sham-operates. There were major contralesional reaching impairments which improved during a 4 week training period, but movements remained significantly abnormal. Anesthetization of the ipsilesional forelimb with lidocaine at this time attenuated the contralesional movement abnormalities. These findings indicate that unilateral ischemic SMC lesions impair skilled reaching behavior in both forelimbs. Furthermore, after partial recovery in the contralesional forelimb, additional improvements can be induced by transient anesthetization of the ipsilesional forelimb. This is consistent with the effects of unilateral anesthetization in humans which have been attributed to the modulation of competitive interhemispheric interactions. The present findings suggest that such interactions are also likely to influence skilled reaching function in rats.     

Task-specific compensation and recovery following focal motor cortex lesion in stressed rats

One reason for the difficulty to develop effective therapies for stroke is that intrinsic factors, such as stress, may critically influence pathological mechanisms and recovery. In cognitive tasks, stress can both exaggerate and alleviate functional loss after focal ischemia in rodents. Using a comprehensive motor assessment in rats, this study examined if chronic stress and corticosterone treatment affect skill recovery and compensation in a task-specific manner. Groups of rats received daily restraint stress or oral corticosterone supplementation for two weeks prior to a focal motor cortex lesion. After lesion, stress and corticosterone treatments continued for three weeks. Motor performance was assessed in two skilled reaching tasks, skilled walking, forelimb inhibition, forelimb asymmetry and open field behavior. The results revealed that persistent stress and elevated corticosterone levels mainly limit motor recovery. Treated animals dropped larger amounts of food in successful reaches and showed exaggerated loss of forelimb inhibition early after lesion. Stress also caused a moderate, but non-significant increase in infarct size. By contrast, stress and corticosterone treatments promoted reaching success and other quantitative measures in the tray reaching task. Comparative analysis revealed that improvements are due to task-specific development of compensatory strategies. These findings suggest that stress and stress hormones may partially facilitate task-specific and adaptive compensatory movement strategies. The observations support the notion that hypothalamic-pituitary-adrenal axis activation may be a key determinant of recovery and motor system plasticity after ischemic stroke.     

Detection of chronic sensorimotor impairments in the ladder rung walking task in rats with endothelin-1-induced mild focal ischemia

A comprehensive evaluation of the effects of neuroprotection, neurogenesis, and compensatory mechanisms on the outcome of ischemic insults requires assessment of morphological and functional parameters. Behavioural tests are essential when recording performance throughout the time course of an experiment and the results bear predictive value in preclinical animal models. The goal of this study was to establish a behavioural test procedure for a model of transient focal ischemia induced by injection of endothelin-1 (eMCAO) that results in relatively mild behavioural deficits. The test protocol used in the present study allows evaluation of quantitative and qualitative impairments in skilled motor performance and is sensitive to detect chronic deficits at chronic post-ischemic time intervals. The ladder rung walking task [J. Neurosci. Methods 115 (2002) 169] is a motor test that assesses skilled walking and measures both forelimb and hindlimb placing, stepping and inter-limb co-ordination. In this study we tested the effect of two different technical variants of endothelin-1 application on infarct volume and motor skills (1) application via pre-implanted guiding cannula in awake animals and (2) via direct injection under halothane anaesthesia. We showed that the ladder rung walking task is sensitive in the assessment of loss of fine motor function after induction of relatively small lesions. In animals with implanted cannulas we found a smaller infarct area and an increase in placement errors prior to ischemia animals with eMCAO under anaesthesia showed a long lasting impairment of the contralateral forelimb up to 4 weeks post-eMCAO.     

Unilateral ischemic sensorimotor cortical damage induces contralesional synaptogenesis and enhances skilled reaching with the ipsilateral forelimb in adult male rats

Unilateral damage to the forelimb representation area of the sensorimotor cortex (SMC) results in a compensatory reliance on the unimpaired (ipsilateral to the lesion) forelimb as well as reorganization of neuronal structure and connectivity in the contralateral motor cortex. Recently, male rats with unilateral electrolytic SMC lesions were found to have enhanced skilled reaching performance with the ipsilesional forelimb compared with sham-operated controls. The present study was performed to determine whether these behavioral findings are replicable using an ischemic lesion and whether there is a link between the enhanced learning and synaptogenesis in motor cortical layer V opposite the trained limb and lesion, as assessed using stereological methods for light and electron microscopy. Rats were given a sham operation or an endothelin-1 (ET-1) induced ischemic SMC lesion. They were then trained for 20 days on a skilled reaching task with the unimpaired limb or received control procedures. As with previous findings using electrolytic lesions, rats with unilateral ischemic SMC lesions performed significantly better using the unimpaired forelimb than did sham-operates. Lesions, but not training, significantly increased the total number of motor cortical layer V synapses per neuron as well as the number of perforated and multisynaptic bouton (MSB) synapses per neuron compared with shams. Thus, in addition to a net increase in synapses, the improved reaching ability was coupled with an increase in synapse subtypes that have previously been linked to enhanced synaptic efficacy. The failure to induce synaptogenesis in layer V with reach training alone is in contrast to previous findings and may be related to training intensity.     

Stress precipitates functional deficits following striatal silent stroke: a synergistic effect

Stress has been linked to structural and functional outcomes after stroke. Moreover, the striatum, both dorsal and ventral, is a vital regulator of stress perception and associated physiological responses. This study investigates potential synergistic effects of focal stroke in the ventrolateral striatum and restraint stress on motor and spatial performance. Adult male Long–Evans rats were pre-trained in a skilled reaching task and randomly assigned to sham, stroke-only, stress-only and stroke + stress conditions. Ventrolateral striatal focal ischemia was induced by endothelin-1 (ET-1) infusion. Rats in stress-only and stroke + stress groups received 21 days of mild restraint stress after stroke. All rats were tested in the skilled reaching task and the ziggurat task (ZT) for post-stroke motor and spatial performance. There was no effect of ventrolateral striatal ischemia or stress alone on motor and spatial performance. Notably, stroke and stress interacted synergistically to reduce reaching success and to disrupt qualitative aspects of movement performance in the absence of histological differences in lesion size. Thus, stress can precipitate behavioural deficits after focal ischemia even in the absence of significant functional deficits on its own. These results emphasize the importance of prevention programmes to control post-stroke levels of stress in clinical populations.     

Behavioral recovery and anatomical plasticity in adult rats after cortical lesion and treatment with monoclonal antibody IN-1

We have previously reported that monoclonal antibody (mAb) IN-1 treatment after ischemic infarct in adult rats results in significant recovery of skilled forelimb use. Such recovery was correlated with axonal outgrowth from the intact, opposite motor cortex into deafferented subcortical motor areas. In the present study, we investigated the effects of mAb IN-1 treatment after adult sensorimotor cortex (SMC) aspiration lesion on behavioral recovery and neuroanatomical plasticity in the corticospinal tract. Adult rats underwent unilateral SMC aspiration lesion and treatment with either mAb IN-1 or a control Ab, or no treatment. Animals were then tested over a 6-week period in the skilled forelimb use task and the skilled ladder rung walking task. We found that animals treated with mAb IN-1 after SMC lesion fully recovered the use of forelimb reaching, but showed no improvement in digit grasping as tested in the skilled forelimb use task. The mAb IN-1 treatment group was also significantly improved as compared to control groups in the skilled ladder rung walking test. Furthermore, neuroanatomical tracing revealed a significant increase in the corticospinal projections into the deafferented motor areas of the spinal cord after mAb IN-1 treatment. These results indicate that treatment with mAb IN-1 after cortical aspiration lesion induces remodeling of motor pathways resulting in recovery in only certain behavioral tasks, suggesting that the cause of brain damage influences behavioral recovery after mAb IN-1 treatment.     

Sequential bilateral striatal lesions have additive effects on single skilled limb use in rats

Unilateral dopamine depletion in rats induced by injection of 6-hydroxydopamine (6-OHDA) into the nigrostriatal system causes permanent impairments in limb use. The disturbances in limb use, including impairments in skilled reaching, are most severe on the side contralateral to the lesion. A number of studies, however, have also described ipsilateral deficits in skilled reaching. The purpose of this study was to investigate the effects of sequential bilateral striatal 6-OHDA lesions on skilled reaching movements in rats to compare the contribution of contra- versus ipsilateral motor control. Rats were trained in a reaching task to grasp food pellets with their preferred paw prior to receiving an intrastriatal 6-OHDA injection on the side contralateral to the preferred paw. The lesion significantly reduced reaching success along with qualitative impairments in limb use. In addition, animals displayed asymmetry in limb use and contraversive rotation bias after an apomorphine challenge. Three weeks later, animals received a second lesion induced by intrastriatal 6-OHDA injection into the hemisphere ipsilateral to the preferred paw. This lesion exaggerated the previous impairments in limb use and further reduced reaching success of the preferred paw. In the ladder rung walking task, additional impairments were found only in the forelimb ipsilateral to the first lesion. The findings of additive effects of sequential bilateral lesions suggest that both the contra- and ipsilateral striatum control single limb use. This supports the notion of bilateral control of skilled forelimb use by the mesostriatal dopaminergic system.     

Unilateral ischemic sensorimotor cortical damage in female rats: forelimb behavioral effects and dendritic structural plasticity in the contralateral homotopic cortex

Previous studies in male rats with unilateral sensorimotor cortical (SMC) damage have demonstrated dendritic structural plasticity in the contralateral homotopic cortex and an enhancement of skilled reaching performance in the forelimb ipsilateral to the lesion compared to sham-operated rats. The purpose of this study was to determine if these findings could be replicated in an ischemic lesion model in female rats. Female rats were given sham operations or unilateral ischemic (endothelin-1 induced) damage in the forelimb representation area of the SMC opposite their preferred forelimb. Animals then received either 20 consecutive days of training on a skilled reaching task with the non-preferred/unimpaired forelimb or no-training control procedures. The surface density of dendrites immunoreactive (IR) for microtubule-associated protein 2 (MAP2) was then measured in the motor cortex opposite the trained limb and/or lesion. Female rats with sufficiently large, but not very small, lesions performed better with the unimpaired forelimb than sham-operated rats on the reaching task. The post-lesion reaching performance was not found to be significantly dependent upon estrous stage at the time of surgery, in agreement with previous studies that failed to find sex or sex-hormone effects after other types of SMC damage. Additionally, there were major laminar-dependent increases in the surface density of MAP2 IR dendrites in the cortex opposite lesions and trained limbs. These findings in female rats are consistent with the dendritic and behavioral changes previously found in male rats. They extend these previous findings by indicating that lesion size is an important variable in the enhancement of reaching performance.     

Motor cortical stimulation promotes synaptic plasticity and behavioral improvements following sensorimotor cortex lesions

Cortical stimulation (CS) as a means to modulate regional activity and excitability in cortex is emerging as a promising approach for facilitating rehabilitative interventions after brain damage, including stroke. In this study, we investigated whether CS-induced functional improvements are linked with synaptic plasticity in peri-infarct cortex and vary with the severity of impairments. Adult rats that were proficient in skilled reaching received subtotal unilateral ischemic sensorimotor cortex (SMC) lesions and implantation of chronic epidural electrodes over remaining motor cortex. Based on the initial magnitude of reaching deficits, rats were divided into severely and moderately impaired subgroups. Beginning two weeks post-surgery, rats received 100 Hz cathodal CS at 50% of movement thresholds or no-stimulation control procedures (NoCS) during 18 days of rehabilitative training on a reaching task. Stereological electron microscopy methods were used to quantify axodendritic synapse subtypes in motor cortical layer V underlying the electrode. In moderately, but not severely impaired rats, CS significantly enhanced recovery of reaching success. Sensitive movement analyses revealed that CS partially normalized reaching movements in both impairment subgroups compared to NoCS. Additionally, both CS subgroups had significantly greater density of axodendritic synapses and moderately impaired CS rats had increases in presumed efficacious synapse subtypes (perforated and multiple synapses) in stimulated cortex compared to NoCS. Synaptic density was positively correlated with post-rehabilitation reaching success. In addition to providing further support that CS can promote functional recovery, these findings suggest that CS-induced functional improvements may be mediated by synaptic structural plasticity in stimulated cortex.     

Attempt-dependent decrease in skilled reaching characterizes the acute postsurgical period following a forelimb motor cortex lesion: an experimental demonstration of learned nonuse in the rat

The notion that shock or diaschisis is a distinctive stage in the recovery process following brain damage has played a formative role in the characterization of brain injury. For example, damage to the forelimb region of motor cortex results in an acute period of behavioural depression in skilled reaching and other skilled actions followed by improved performance mediated by compensatory movements. Whereas the progression of improvement and the use of compensatory movements in the chronic period of recovery is well-documented, temporal aspects of behaviour during the acute period of depression of behaviour are relatively unstudied. The present study examined the temporal scheduling of reach-attempts by rats attempting to gain single pellets of food from a shelf in a skilled reaching task. Pretrained rats received contralateral-to-the-pretrained limb forelimb motor cortex lesions. Control lesions included contralateral-to-the-pretrained limb parietal cortex lesions, or ipsilateral-to-the-pretrained limb motor cortex lesions. Frame-by-frame video analysis of behaviour showed a decrease in reaching attempts as a function of successive approaches and attempts to grasp the food over the first few postsurgical days in rats with contralateral-to-the-pretrained limb motor cortex lesions. A similar approach-dependent decrease in attempts did not occur after parietal or ipsilateral-to-the-pretrained limb motor cortex lesions. The decrease in responding occurred only during acute testing and was not observed in rats first tested after 8 days of postoperative recovery. The findings are discussed in relation to the ideas that: (1) the stroke subject is an active participant in modifying behaviour to cope with injury; (2) learned nonuse contributes to behaviour in the acute postinjury period following motor cortex injury; (3) diaschisis inadequately accounts for poststoke behaviour.     

Epidural cortical stimulation enhances motor function after sensorimotor cortical infarcts in rats

This study examined whether epidurally delivered cortical electrical stimulation (CS) improves the efficacy of motor rehabilitative training and alters neuronal density and/or cell proliferation in perilesion cortex following ischemic sensorimotor cortex (SMC) lesions. Adult rats were pre-trained on a skilled reaching task and then received partial unilateral SMC lesions and implantation of electrodes over the remaining SMC. Ten to fourteen days later, rats received daily reach training concurrent with anodal or cathodal 100 Hz CS or no stimulation (NoCS) for 18 days. To label newly generated cells, bromodeoxyuridine (BrdU; 50 mg/kg) was administered every third day of training. Both anodal and cathodal CS robustly enhanced reaching performance compared to NoCS controls. Neuronal density in the perilesion cortex was significantly increased in the cathodal CS group compared to the NoCS group. There were no significant group differences in BrdU-labeled cell density in ipsilesional cortex. Staining with Fluoro-Jade-B indicated that neurons continue to degenerate near the infarct at the time when cortical stimulation and rehabilitation were initiated. These data indicate that epidurally delivered CS greatly improves the efficacy of rehabilitative reach training following SMC damage and raise the possibility that cathodal CS may influence neuronal survival in perilesion cortex.     

Contralesional neural plasticity and functional changes in the less-affected forelimb after large and small cortical infarcts in rats

Some studies have found that unilateral cerebral damage produces significant deficits in the ipsilesional, "less-affected", body side. Other studies have found that such damage results in a paradoxical hyperfunctionality of the ipsilesional body side and a facilitation of learning-induced neuroplastic changes in the contralesional motor cortex. The purpose of this study was to determine whether these effects co-exist and/or vary with lesion severity. After small or large unilateral ischemic lesions of the sensorimotor cortex (SMC) or sham operations, adult male rats were trained for 20 days to acquire a motor task, skilled reaching for food, for the first time with the ipsilesional forelimb. Analyses of movement patterns indicated lesion-size-dependent ipsilesional abnormalities in grasping, retrieving and releasing food pellets. Despite these impairments, success rates were significantly increased and aiming errors reduced in lesion groups compared with sham operates. Performance was best in rats with small lesions that had more minor ipsilesional impairments. In the motor cortex contralateral to the lesion and trained limb, there were significant increases in the density of dendrites immunoreactive for microtubule-associated protein-2 (MAP2) and of N-methyl-D-aspartate receptor subunit 1 (NMDAR1) immunoreactivity compared with sham operates. These effects were correlated with reaching performance. Therefore, enhanced motor skill learning in the "less-affected" forelimb and contralesional neuroplastic changes are muted after larger lesions and co-exist with ipsilesional impairments. These effects may be related to a denervation-induced neural restructuring of the contralesional cortex that both disrupts pre-existing motor engrams and facilitates the establishment of new ones.     

Delayed treatment with monoclonal antibody IN-1 1 week after stroke results in recovery of function and corticorubral plasticity in adult rats.

Neuronal death due to ischemic stroke results in permanent deficits in sensory, language, and motor functions. The growth-restrictive environment of the adult central nervous system (CNS) is an obstacle to functional recovery after stroke and other CNS injuries. In this regard, Nogo-A is a potent neurite growth-inhibitory protein known to restrict neuronal plasticity in adults. Previously, we have found that treatment with monoclonal antibody (mAb) IN-1 to neutralize Nogo-A immediately after stroke enhanced motor cortico-efferent plasticity and recovery of skilled forelimb function in rats. However, immediate treatment for stroke is often not clinically feasible. Thus, the present study was undertaken to determine whether cortico-efferent plasticity and functional recovery would occur if treatment with mAb IN-1 was delayed 1 week after stroke. Adult rats were trained on a forelimb-reaching task, and the middle cerebral artery was occluded to induce focal cerebral ischemia to the forelimb sensorimotor cortex. After 1 week, animals received mAb IN-1 treatment, control antibody, or no treatment, and were tested for 9 more weeks. To assess cortico-efferent plasticity, the sensorimotor cortex opposite the stroke lesion was injected with an anterograde neuroanatomical tracer. Behavioral analysis demonstrated a recovery of skilled forelimb function, and anatomical studies revealed neuroplasticity at the level of the red nucleus in animals treated with mAb IN-1, thus demonstrating the efficacy of this treatment even if administered 1 week after stroke.     

Stress accelerates neural degeneration and exaggerates motor symptoms in a rat model of Parkinson's disease

The causes of most cases of Parkinson's disease (PD) are still poorly understood. Here we show that chronic stress and elevated corticosterone levels exaggerate motor deficits and neurodegenerative events in a Parkinson's disease rat model. Animals were tested in skilled and non-skilled movement while being exposed to daily restraint stress or oral corticosterone treatment. Stress and corticosterone compromised normal motor function and exaggerated motor deficits caused by unilateral 6-hydroxydopamine lesion of the nigrostriatal bundle. Moreover, stress and corticosterone treatments diminished the ability to acquire compensatory strategies in limb use during skilled reaching and skilled walking. In contrast, lesion control animals were able to significantly improve in the ability of skilled limb use during the repeated test sessions. The exaggerated motor impairments in stress-treated animals were related to accelerated loss of midbrain dopamine-producing neurons during the first week postlesion. Correlation analysis revealed a significant connection between loss of tyrosine hydroxylase-positive cells and increase in Fluoro-Jade-positive cells only in stress- and corticosterone-treated animals. Furthermore, stress and elevated corticosterone levels caused greater permanent loss of midbrain neurons than found in non-treated lesion animals. These findings demonstrate that stress and elevated corticosterone levels can exaggerate nigral neuronal loss and motor symptoms in a rat analogue of PD. It is therefore possible that stress represents a key factor in the pathogenesis of human PD by impeding functional and structural compensation and exaggerating neurodegenerative processes.     

Bilateral alteration in stepping pattern after unilateral motor cortex injury: a new test strategy for analysis of skilled limb movements in neurological mouse models

Mice are becoming increasingly popular to model neurological disease and motor system dysfunction. For evaluation of discrete, chronic motor impairments, skilled limb movements represent a valuable extension of standard mouse test batteries. This study introduces an efficient and sensitive test strategy for comprehensive assessment of skilled fore- and hind-limb stepping in mice. Adult C57BL/6 mice were trained and video-recorded in two walking tasks, the widely used rotorod test and a new ladder rung task. The animals then received a unilateral ischemic lesion in the motor cortex forelimb and hind limb area and were video-recorded on days 12 and 26 post-lesion. Forelimb and hind limb stepping movements were rated using a combination of endpoint measures and qualitative assessment. The results showed that while animals maintained a weight-supported gait, posture and stepping movements were abnormal at both post-operative intervals. The rotorod analysis revealed stepping deficits in both forelimbs that led to adoption of compensatory movement strategies. The ladder rung task revealed stepping errors in ipsi- and contralateral fore- and hind-limbs. The findings demonstrate that this test strategy provides comprehensive assessment of motor impairments in mice and that qualitative movement analysis is a valuable tool for elaborating subtle motor disturbances.     

Effects of combined dorsolateral and dorsal funicular lesions on sensorimotor behaviour in rats

The purpose of this research was to investigate the compensatory role of undamaged spinal pathways after partial spinal injury in rats. We have previously shown that bilateral lesions of the dorsal funiculus (DF) at the cervical level caused changes in overground and skilled locomotion that affected the forelimbs more than the hindlimbs. The same lesions also caused fore-paw deficits during a skilled pellet retrieval task (Kanagal and Muir, 2007). In contrast, bilateral cervical lesions of the dorsolateral funiculus (DLF) caused alterations in overground and skilled locomotion that were most marked in the hindlimbs rather than the forelimbs, but also caused fore-paw deficits during skilled pellet retrieval (Muir et al., 2007). We hypothesized that the relative lack of forelimb deficits during locomotion after DLF lesions was due to compensatory input arising from intact pathways in the DF. We tested this hypothesis in the present study by performing bilateral DF lesions in animals in which both DLFs had been transected 6 weeks previously. These secondary DF lesions involved either only ascending sensory pathways (DLF+ASP group) in the DF, i.e. sparing the corticospinal tract (CST), or involved both the ASP and the CST (DLF+DF group). All animals were assessed during overground locomotion, while crossing a horizontal ladder and during a pellet retrieval task. During overground locomotion, both groups moved with slightly altered forces and timing in both forelimbs and hindlimbs. During both ladder crossing and reaching, secondary lesions to DF (with or without CST) exacerbated the deficits seen after initial DLF lesions and additionally caused changes in the manner in which the rats used their forelimbs during reaching. Nevertheless, the relative magnitude of the deficits indicates that DF pathways in rats likely do not compensate for loss of DLF pathways during the execution of locomotor tasks, though there is indirect evidence that DLF-lesioned rats might rely more on ascending sensory pathways in the DF during skilled forelimb movements. The plastic changes mediating recovery are therefore necessarily occurring in other regions of the CNS, and, importantly, need time to develop, because animals with DLF+DF lesions performed simultaneously displayed marked functional deficits and were unable to use their forelimbs for skilled locomotion or reaching.     

Silent stroke in patients with transient ischemic attack or minor ischemic stroke. The Dutch TIA Trial Study Group.

BACKGROUND AND PURPOSE: We studied silent stroke (i.e., infarcts on computed tomographic scan not related to later symptoms) in patients after transient ischemic attack or minor ischemic stroke. METHODS: Ours is a cross-sectional study of 2,329 patients who were randomized in a secondary prevention trial after transient ischemic attack or minor ischemic stroke and had no residual deficit after the qualifying event. RESULTS: Silent stroke was observed in 13% of the 2,329 patients. Lacunes formed 79%, cortical lesions 14%, and border zone lesions 7% of all silent strokes. Silent lacunes were most often located in the basal ganglia and symptomatic lacunes most often in the corona radiata. Age, hypertension, and current cigarette smoking were related to the presence of silent stroke. Silent stroke was equally common in different types of transient ischemic attack, including transient monocular blindness. Residual symptoms of any kind were more common in patients with silent stroke than in those without. CONCLUSIONS: Because only the sites of silent stroke infarcts differed slightly from those of symptomatic infarcts and the frequency of vascular risk factors was similar to that of symptomatic infarcts, silent stroke may have the same bearing on future risk as known prior stroke.