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1.
OBJECTIVE: To examine the relation between depressive symptoms and specific cognitive functions in patients with a recent stroke and to examine associations with lesion characteristics. METHODS: We studied 126 of 183 consecutive patients within 3 weeks after a first-ever symptomatic stroke (mean interval, 8.3+/-4.3 days). Presence and severity of depressive symptoms was assessed with the Montgomery Asberg Depression Rating Scale. Neuropsychological functioning was examined by means of a detailed neuropsychological examination covering six cognitive domains. We included a healthy control group (N=75) to obtain normative data for the neuropsychological examination. Functional impairment was measured with the modified Barthel Index and the modified Rankin Scale. Symptomatic and preexistent lesion characteristics were determined on CT or MRI. RESULTS: Of the included patients, 40% demonstrated mild and 12% moderate to severe depressive symptoms. Severity of depressive symptoms was related to lesion volume (p=0.008), functional impairment (all p<0.004), and degree of overall cognitive impairment (p=0.005). After adjustment for lesion size, a specific neuropsychological profile emerged in patients with moderate to severe depressive symptoms, affecting primarily memory, visual perception, and language (all p<0.05). No association was found between severity of depressive symptoms and lesion location, presence of preexistent lesions (white matter lesions and silent infarcts), and demographic factors (age, education, and gender). CONCLUSIONS: Moderate or severe symptoms of depression in the early stage poststroke are associated with a specific pattern of cognitive impairment, lesion size, and functional status. We suggest that depressive symptoms early after stroke are, at least in part, a reactive phenomenon secondary to severe cognitive and functional deficits.  相似文献   

2.
OBJECTIVE: The aim of the present study was to examine the predictive value of cognitive impairment in the acute phase after stroke as a risk factor for long-term (six to ten months after stroke) depressive symptoms (DS) and a reduced quality of life (QOL), independent of demographic and neurological predictors. METHODS: We evaluated 143 patients within the first 3 weeks post-stroke. Predictor variables included domain-specific cognitive function, demographic data, vascular risk factors, lesion characteristics, and clinical factors. Predictor variables associated with long-term DS (Montgomery Asberg Depression Rating Scale >or=7) and QOL (Stroke-Specific Quality of Life Scale) were identified with multiple logistic and linear regression. RESULTS: Long-term DS were independently predicted by cognitive impairment at baseline, DS at baseline, female sex, diabetes mellitus, and previous TIA(s). Cognitive impairment, increasing age, and functional dependence predicted a reduced QOL, whereas hypercholesterolaemia predicted a better QOL. Among all cognitive disorders, unilateral neglect was the greatest risk factor for DS after 6 months, whereas a disorder in visual perception and construction affected QOL the most. CONCLUSIONS: Cognitive impairment and vascular risk factors are important predictors of long-term DS and QOL after stroke. The prognostic value of cognition suggests a reactive component in the development or continuation of long-term DS.  相似文献   

3.
目的:探索抑郁障碍患者认知功能损害的特点,以及与临床特征和症状严重程度的关系。方法:采用成套神经认知测试系统(CANTAB)对90例抑郁障碍患者及100例健康对照者进行认知功能测试,包括视觉记忆、持续注意、工作记忆与执行功能。结果:患者组所有认知功能与对照组相比,差异有统计学意义(P0.05)。抑郁发作次数与视觉记忆、持续注意负相关(P0.01);单次抑郁发作持续时间与持续注意、执行功能负相关(P均0.01)。汉密尔顿抑郁量表的认知障碍因子与视觉记忆负相关(P均0.01);焦虑/躯体化因子、阻滞因子与持续注意负相关(P均0.05)。结论:抑郁障碍患者存在广泛的认知功能损害,临床特征和症状严重度对认识功能损害存在差异性的影响。  相似文献   

4.
The aim of the study was to determine the course of cognitive functioning within the subacute phase (< 4 months) after stroke during rehabilitation. Stroke patients admitted to a rehabilitation centre were submitted to a neuropsychological examination on admission (1 month post-stroke) and upon discharge (4 months post-stroke). Cognitive domains studied were attention, executive functioning, memory, and visual attention. Forty-two patients (mean age?=?57.1 years; SD?=?7.7) participated. At admission more than half of the patients showed deficits in attention and memory. Patients improved significantly on these domains; the largest improvement was seen in the domain of visual attention, while executive functioning did not improve significantly. A differential course of cognitive functioning was found in the subacute phase after stroke. The prognosis of visual attention is the most prominent.  相似文献   

5.
Recent evidence on amusia suggests that our ability to perceive music might be based on the same neural resources that underlie other higher cognitive functions, such as speech perception and spatial processing. We studied the neural correlates of acquired amusia by performing extensive neuropsychological assessments on 53 stroke patients with a left or right hemisphere middle cerebral artery (MCA) stroke 1 week, 3 months, and 6 months after the stroke. In addition, structural magnetic resonance imaging (MRI) was performed on all patients 1 week and 6 months post-stroke. Based on their performance on a shortened version of the Montreal Battery of Evaluation of Amusia (MBEA), the patients were classified as amusic (n = 32) or non-amusic (n = 21). MRI results showed that the incidence of auditory cortex and frontal lobe damage was significantly higher in the amusic group than in the non-amusic group, but the two groups did not differ in respect to lesion laterality. Cognitively, amusia was associated with general deficits in working memory and learning, semantic fluency, executive functioning, and visuospatial cognition, as well as hemisphere-specific deficits in verbal comprehension, mental flexibility, and visuospatial attention (unilateral spatial neglect). Moreover, the recovery of music perception ability was related to the recovery of verbal learning, visuospatial perception and attention, and focused attention, especially in amusic patients. Together, these results suggest the ability to perceive music is closely linked to other higher cognitive functions.  相似文献   

6.
Mild cognitive impairment (MCI) is considered as the early stage of dementia which currently has no effective treatments. Reducing progression of cognitive decline at the MCI stage could be an important strategy for preventing conversion to dementia. The goal of this work was to screen for clinical predictors indicating the prognosis of MCI comprehensively; therefore, we assumed vascular risk factors (VRFs), carotid stenosis, and white matter changes (WMC) to be independent predictors. A total of 257 patients with MCI underwent collection of VRF information, neuropsychological evaluation, computed tomography angiography (CTA) to investigate carotid stenosis, and magnetic resonance imaging (MRI) to identify severity of WMC. After a 3-year follow-up period, the neuropsychological evaluation, CTA, and MRI were repeated to assess the progression of cognitive decline, carotid stenosis, and WMC. The conversion rate from MCI to dementia was 11.65% per year, and the conversion rate from MCI to Alzheimer's disease was 7.05% per year in our cohort. Cognitive decline (in terms of changes in Mini Mental State Examination scores) was associated with diabetes mellitus (p = 0.004), baseline WMC severity (p < 0.001), baseline carotid stenosis (p < 0.001), and WMC severity change (p < 0.001). Besides, diabetes, baseline WMC severity, baseline moderate-to-severe carotid stenosis, and carotid stenosis change during follow-up were predictors of conversion from MCI to dementia. Given the potential clinical predictors, our findings could imply that controlling blood glucose, removing carotid stenosis, and improving cerebral perfusion could be effective measures to delay cognitive decline in patients with MCI and prevent conversion from MCI to dementia.  相似文献   

7.
BACKGROUND: Cognitive dysfunction is the most common form of neurologic impairment after subarachnoid hemorrhage (SAH). OBJECTIVE: To evaluate the impact of global and domain-specific cognitive impairment on functional recovery and quality of life (QOL) after SAH. METHODS: One hundred thirteen patients (mean age 49 years; 68% women) were evaluated 3 months after SAH. Three simple tests of global mental status and neuropsychological tests to assess seven specific cognitive domains were administered. Four aspects of outcome (global handicap, disability, emotional status, and QOL) were compared between cognitively impaired and unimpaired patients with analysis-of-covariance models controlling for age, race/ethnicity, and education. Multiple linear regression was used to evaluate the relative contribution of global and domain-specific cognitive status for predicting concurrent modified Rankin Scale (mRS) and Sickness Impact Profile (SIP) scores. RESULTS: Impairment of global mental status on the Telephone Interview of Cognitive Status (TICS) was associated with poor performance in all seven cognitive domains (all p < 0.0005) and was the only cognitive measure associated with poor recovery in all four aspects of outcome (all p < or = 0.005). Cognitive impairment in four specific domains was also associated with functional disability or reduced QOL. After accounting for global cognitive impairment with the TICS, however, neuropsychological testing did not contribute additional predictive value for concurrent mRS or SIP total scores. CONCLUSIONS: Cognitive impairment impacts broadly on functional status, emotional health, and QOL after SAH. The TICS may be a useful alternative to more detailed neuropsychological testing for detecting clinically relevant global cognitive impairment after SAH.  相似文献   

8.
ObjectiveTo investigate whether cognitive reserve modifies the relationship between functional connectivity, lesion volume, stroke severity and upper-limb motor impairment and recovery in stroke survivors.MethodsTen patients with first-ever ischemic middle cerebral artery stroke completed the Cognitive Reserve Index Questionnaire at baseline. Upper-limb motor impairment and functional connectivity were assessed using the Fugl-Meyer Assessment and electroencephalography respectively at baseline and 3-months post-stroke. A debiased weighted phase lag index was computed to estimate functional connectivity between electrodes. Partial least squares (PLS) regression identified a connectivity model that maximally predicted variance in the degree of upper-limb impairment. Regression models were generated to determine whether cognitive reserve modified the relationship between neural function (functional connectivity), neural injury (lesion volume), stroke severity (National Institutes of Health Stroke Scale) and upper-limb motor impairment at baseline and recovery at 3-months (Fugl-Meyer Assessment).ResultsThe addition of cognitive reserve to a regression model with a dependent variable of upper-limb motor recovery and independent variables of functional connectivity between the ipsilesional motor cortex and parietal cortex, stroke severity and lesion volume improved model efficiency (?BIC=-7.07) despite not reaching statistical significance (R2=0.90, p=0.07). Cognitive reserve did not appear to improve regression models examining motor impairment at baseline.ConclusionsPreliminary observations suggest cognitive reserve might modify the relationship between neural function, neural injury, stroke severity and upper-limb motor recovery. Further investigation of cognitive reserve in motor recovery post-stroke appears warranted.  相似文献   

9.
Moyamoya Disease (MMD) is a rare cerebrovascular disorder which can have significant cognitive consequences. The aim of the current study was to describe comprehensively the domain-specific cognitive profile of adult patients with MMD and to assess whether this changes in the absence of recurrent stroke over long-term follow-up. Comprehensive neuropsychological assessment covering seven cognitive domains was conducted on 61 adult patients with MMD at baseline and then at up to 3 further time points during follow up (median=2.31, 4.87 and 7.12 years). Although 27 patients had had prior surgical revasculariation, none had surgery between neuropsychological assessments. Cognitive impairment was common. At baseline, impairment in executive functions was most frequent (57%), followed by performance IQ (36%), speed of information processing (31%) and visual memory (30%). We found that the neuropsychological profile remains broadly stable over long-term follow-up with no clear indication of improvement or significant decline. The pattern of impairment also did not differ depending on age of onset or whether there was a history of either prior stroke at presentation or revascularisation surgery at presentation.  相似文献   

10.
Cognitive impairments are frequent in Multiple sclerosis (MS). However, most studies about efficacy of cognitive rehabilitation interventions have been criticized in terms of methods and/or design. The aim of this study is to evaluate the efficacy of cognitive rehabilitation in MS patients with a cognitive intervention (ProCogSEP* program), compared to a control intervention (discussion program). Twenty MS patients have completed this simple blind study: 10 patients followed 13 sessions (2 hours) of the ProCog-SEP1 program. Ten other patients followed 13 sessions (2 hours) of a discussion program (Control Group). All patients underwent neuropsychological assessment, before and after their program, in order to evaluate cognitive functions. Two neuropsychologists respectively assessed the patients and conducted the group sessions. Compared to its own baseline, ProCog-SEP Group show improvements in verbal memory [free recall (p = .02), learning (p = .002)], in visual memory [free (p = .05) and delayed recall (p = .007)], in working-memory (p = .03), in verbal fluency (p = .05) and in language (p = .01). Inter group analysis show a benefit of cognitive program mainly in verbal and visual memory, and in verbal fluencies. These results support the interest of a cognitive therapeutic management of MS patients.  相似文献   

11.
IntroductionVisual dysfunction and cognitive impairment are common in Parkinson's disease (PD) but the precise contribution of lower-level visual impairment to visual-input based cognitive performance has not been extensively characterized in PD.MethodsWe included 49 PD patients and 22 healthy controls (HC). Lower-level visual function tests [high and low contrast visual acuity (HCVA and LCVA) and contrast sensitivity (CS)] and a neuropsychological battery (involving visual cognition) were performed. Pairwise correlations between lower-level visual functions and visual cognition were computed and stepwise linear regressions were fitted introducing age, Geriatric Depression Scale, and lower-level visual functions in the model to calculate their predicted effect on visual cognition.ResultsCompared to controls, patients presented a significant impairment in all cognitive domains (visual attention, visual processing speed and visual perception, visuospatial abilities, visuoconstructive abilities, and visual memory), and lower-level visual functions. HCVA and LCVA were significantly associated with visual cognition in PD. HCVA explained up to 49.3% and 34.2% of the variability in visual perception and visuospatial abilities, respectively, whereas LCVA was mainly associated with short- and long-term visual memory and visuospatial abilities.ConclusionLower-level visual dysfunction is highly associated with cognitive performance in PD, when cognitive tests are based on visual input. Our results support that lower-level visual functions should be considered when assessing cognitive status of PD patients and might be useful for predicting cognitive deterioration.  相似文献   

12.
ObjectiveLongitudinal follow-up of neurocognitive functioning in people with pediatric bipolar disorder (PBD) was conducted to characterize the developmental trajectory of cognitive disabilities in this disorder.MethodPatients with PBD (n = 26) and controls (HC; n = 17; mean age 11.66 ± 2.70 years) completed cognitive testing at baseline and then again at a 3-year follow-up. Groups were matched at baseline on age, sex, race, parental socioeconomic status, general intelligence, and single-word reading ability. The PBD group received treatment guided by a standardized medication algorithm during the 3-year period. A battery of neuropsychological tests was administered to assess attention, executive function, working memory, verbal memory, visual memory, and visuospatial perception at baseline and follow-up.ResultsAt baseline and follow-up, the patients showed deficits in all of the examined domains. At 3-year follow-up, developmental progress in executive functions and verbal memory was significantly less in the patients with PBD than in the HC. Improvement on attention, working memory, visual memory, and visuospatial perception tasks in the patients with PBD was comparable to that of the HC, but the patients with PBD remained impaired in all domains relative to the HC.ConclusionsThe developmental delay in some neurocognitive functioning in PBD suggests that the illness disrupts cognitive development with potential lifelong implications for reduced functional ability. Treating bipolar symptoms does not seem to prevent the lag in cognitive development. This dysmaturation may be a direct effect of the illness on brain function, or it may represent indirect consequences of psychopathology or medications on cognitive development.  相似文献   

13.
At present, there is poor accuracy in assessing cognitive and vegetative symptoms in depression using clinician or self-rated measures, suggesting the need for development of standardized tasks to assess these functions. The current study assessed the psychometric properties and diagnostic specificity of a brief neuropsychological screening battery designed to assess core signs of depression; psychomotor retardation, attention and executive functioning difficulties, and impaired emotion perception within an outpatient psychiatry setting. Three hundred eighty-four patients with mood disorders and 77 healthy volunteers participated. A large percentage of patients met diagnostic criteria for Major Depressive Disorder alone (49%) or with another comorbid psychiatric disorder (24%). A brief, 25-min battery of computer-based tests was administered to control participants and patients measuring the constructs of inhibitory control, attention, visual perception, and both executive and visual processing speed. The patient groups performed significantly worse than the control group regardless of diagnosis on visual perception and attention accuracy and processing speed factors. Surprisingly, the anxiety disorder group performed better than several other psychiatric disorder groups in inhibitory control accuracy. Developing valid and reliable measures of cognitive signs in mood disorders creates excellent opportunities for tracking cognitive status prior to initiation of treatment, and allows for reliable retest following treatment.  相似文献   

14.
目的 研究急性脑卒中患者中认知功能障碍对远期产生抑郁症状(DS)的预测价值.方法 根据入选排除标准选择143例脑卒中后前3周的病人,选择预测变量为早期认知功能、人口基性特征、血管危险因素、病变部位、抑郁症状、神经功能缺损及日常生活能力,因变量为入组后6~10个月后远期抑郁症状(蒙哥马利抑郁量表评分>7分)进行多元Log...  相似文献   

15.
A prospective study of cognitive impairment in ALS   总被引:9,自引:0,他引:9  
Strong MJ  Grace GM  Orange JB  Leeper HA  Menon RS  Aere C 《Neurology》1999,53(8):1665-1670
OBJECTIVE: To characterize prospectively the cognitive profile in ALS. METHODS: Clinically definite ALS patients (11 men, 2 women), age 39.9 to 74.0 years (mean age, 54.2 +/- 9.6 years; mean disease duration, 21.1 +/- 10.5 months) underwent neuropsychologic, language, and speech testing followed by MR 1H spectroscopy (4 T). Five spousal control subjects completed an identical protocol. Eight ALS patients participated in follow-up studies at a 6-month interval. RESULTS: Relative to control subjects, ALS patients showed mild impairment in word generation, recognition memory (faces), and motor-free visual perception. Bulbar-onset patients showed greater impairment in a number of measures (working memory, problem solving/cognitive flexibility, visual perception, and recognition memory for words and faces), and cognitive impairment appeared more progressive over time. ALS patients demonstrated anomia on a confrontation naming test, with no significant problems following commands or repeating. Speech motor performance scores and intelligibility scores were not significantly different. No significant declines in forced vital capacity, forced expiratory volume, or peak expiratory flow rates were observed. Although normal at initial testing (T1), MR 1H spectroscopy demonstrated a reduction of the N-acetylaspartate/creatine (NAA/Cr) ratio in the nondominant precentral motor strip across the two testing intervals. In contrast, the NAA/Cr ratio obtained from the anterior cingulate gyrus at T1 was already reduced in bulbar-onset patients (p < 0.001), whereas no deficits were observed in limb-onset individuals in the same region. CONCLUSIONS: Bulbar-onset ALS patients with cognitive impairments and neuronal loss in the anterior cingulate gyrus subsequently developed more profound neuropsychological dysfunction whereas both language and speech capabilities remained relatively preserved. Of note, the absence of bulbar signs did not predict an absence of cognitive decline.  相似文献   

16.
BACKGROUND: Although cognitive impairment early after stroke is a powerful predictor of long-term functional dependence and dementia, little is known about the characteristics and determinants of cognitive dysfunction in acute stroke. METHODS: We administered a neuropsychological examination covering 7 cognitive domains to 190 patients within 3 weeks after a first stroke. We also assembled lesion characteristics, clinical factors at admission, demographic characteristics and vascular risk factors. Multivariate logistic regression adjusted for age, gender and education was performed to examine determinants of acute cognitive impairment. RESULTS: Overall, 74% of patients with a cortical stroke, 46% with a subcortical stroke and 43% with an infratentorial stroke demonstrated acute cognitive impairment.Disorders in executive functioning (39%) and visual perception/construction (38%) were the most common. The prevalence and severity of deficits in executive functioning, language, verbal memory and abstract reasoning was more pronounced following left compared to right cortical stroke (all p < 0.05). Intracerebral haemorrhage (OR = 5.6; 95% CI = 1.2-25.4) and cortical involvement of the stroke (OR = 3.6; 95%, CI = 1.3-9.9) were independent determinants of acute cognitive impairment, whereas premorbid moderate alcohol consumption exerted a protective effect (OR = 0.4; 95% CI = 0.1-1.1). CONCLUSIONS: Cognitive impairment is common in the first weeks after stroke, with executive and perceptual disorders being the most frequent. Intracerebral haemorrhage, cortical involvement of the lesion and premorbid moderate alcohol consumption are independently associated with acute cognitive impairment.  相似文献   

17.
OBJECTIVE: To compare children with comorbid anxiety disorders (ANX) and attention-deficit hyperactivity disorder (ADHD) with children with either pure disorder and normal controls on 2 cognitive measures to elucidate the cognitive basis of this comorbidity. METHOD: Four groups of children aged 8 to 12 years (n = 64 total) were assessed: ANX, ADHD, both conditions (comorbid group), and neither condition (normal control group). Groups were compared on 2 cognitive measures: a measure of auditory emotional perception (dichotic listening task) and a measure of response inhibition (stop task), chosen for their relative specificity for ANX and ADHD, respectively, in previous studies. RESULTS: Multivariate analyses of variance revealed significant group differences on the dichotic listening task (p < .05), with the comorbid group differing from the control group on emotion targets (p < .01) and the ADHD group differing from the control group on word targets (p < .05). On the stop task, the ADHD group appeared slower than the other diagnostic groups on both go and stop-signal reaction times, but differences were not significant. CONCLUSIONS: In this study, children with comorbid ANX and ADHD showed reduced auditory emotion recognition relative to controls but did not show response inhibition deficits. Thus they appeared cognitively distinct from children with either pure disorder.  相似文献   

18.
Background: For long-term stroke survivors, objective neuropsychological impairments and subjective cognitive difficulties are common, and may contribute to ongoing difficulties in community reintegration. However, subjective cognitive complaints have been as much associated with low mood as with actual cognitive performance.

Objective: The objective of our study was to investigate the extent to which subjective cognitive complaints predicted community reintegration following a stroke, and whether this relationship would be mediated by emotional status.

Methods: Using a cross-sectional design, patients with a primary diagnosis of stroke (n = 102; age range 25–89 years) were recruited from the register of a neurological rehabilitation service if they were at least 6 months post-stroke and had been discharged home following the stroke. Exclusions included history of dementia, co-morbid psychiatric or neurological disorder, or significant aphasia. Assessments included the Subjective Cognitive Complaints Questionnaire, the Community Integration Questionnaire, and the Depression Anxiety and Stress Scale.

Results: Subjective cognitive complaints were common, with moderate to high levels of complaint most frequent for working memory (58.9%), and information processing speed (53%). Subjective cognitive complaints were significantly associated with social integration (r = ?.23, p < .05). However, examination of relationships using statistical mediation revealed that depressive symptoms fully mediated the relationship between subjective cognitive complaints and social integration.

Conclusions: Subjective cognitive complaints are common in long-term outcome following stroke and predict difficulty in community reintegration. However, this relationship is mediated by variation in emotional status. Therefore, addressing cognitive complaints through cognitive rehabilitation programs that include components to improve mood (for example, building self-efficacy or confidence) may also improve community reintegration post-stroke.  相似文献   

19.
Assessment of time perception: the effect of aging.   总被引:1,自引:0,他引:1  
Studies concerning time perception lack a validated assessment tool and a consensual "gold-standard" measure. Moreover, the present evidence suggests modification of timing with aging. This study aimed to develop and validate a neuropsychological tool to measure time perception and to study temporal perception with aging. Eighty-six healthy participants, aged 15-90 years old, were asked to verbally estimate and produce empty intervals signaled by auditory beeps, of 7-, 32-, and 58-s duration. Two tests were used as "gold-standards": estimation of the duration of time necessary to draw a clock ("clock time") and estimation of the duration of neuropsychological evaluation ("global time"). Results showed a correlation between estimation and production (p < .01) and a correlation between estimation or production and "global time" (p < .01). The correlation between either estimation or production and age (p < .01), suggested a faster "internal-clock" in the older participants. However, this finding lost significance when controlled for literacy. The results suggest that these tests are potentially a useful tool to measure subjective perception of time. They also corroborate the hypothesis of a change in subjective time perception with aging. It was not possible to conclude if this effect was a specific result of aging or biased by the interference of literacy.  相似文献   

20.
Summary: Purpose: To determine possible cognitive and behavioral effects of antiepileptic drug (AED) therapy by assessing children with newly diagnosed epilepsy before and after initiation of treatment. A comparison group of children with diabetes mellitus (DM) was included to control for the effects of practice, maturation, and chronic illness.
Methods: Baseline neuropsychological assessments were completed for children with epilepsy (n = 37) and children with DM (n = 26) recruited through outpatient clinics at a regional children's hospital. Children were reevaluated 6 months from baseline testing. At follow-up, children with epilepsy had therapeutic AED levels and controlled seizures. Statistical analysis included a between-group repeated measures ANCOVA with pretest scores serving as the covariate.
Results: Significant differences between groups were not found for any cognitive or behavioral factors, including attention (p < 0.24), immediate memory (p < 0.24), delayed memory (p < 0.10), complex motor speed (p < 0.19), or behavior problems (p < 0.89).
Conclusions: Changes in performance on cognitive and behavioral measures were not different for children treated with AEDs and controls. Although adverse effects may be associated with prolonged treatment, results would not suggest adverse effects from AED monotherapy during the first 6 months of therapy.  相似文献   

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