A two year longitudinal study of poststroke mood disorders: prognostic factors related to one and two year outcome

In a prospective study of mood disorders in 103 stroke patients, we examined the predictive value of affective, cognitive, social and neurologic variables obtained in-hospital and at six months poststroke in terms of outcome as determined by the same measures at one and two years follow-up. The following factors were found to have prognostic significance: 1) Lesion Location: proximity of the lesion on CT scan to the frontal pole in patients with left anterior infarcts showed a strong positive relationship with severity of depression at one year but not at two years poststroke. 2) Affective Status: depression (in-hospital and at 6 months) strongly predicted depression at one year but not at two years poststroke. Additionally, in-hospital depression significantly correlated with physical impairment at two years, while depression at six months bore a moderate relationship to physical impairment at one year. 3) Physical Impairment: impairment in activities of daily living in-hospital bore a modest relationship to depression at one year while such impairment at six months correlated strongly with depression at both one and two years. These findings may reflect the natural course of major depression which remits between one and two years poststroke. Although stroke lesion location is the strongest predictor of subsequent depression, there appears to be a reciprocal relationship between physical impairment and depression (i.e., depression predicts impairment and impairment predicts depression). Since poststroke depressions are amenable to therapeutic intervention, these prognostic factors may have implications for the treatment and rehabilitation of stroke patients.     

Risk factors for and correlates of poststroke depression following discontinuation of antidepressants

The authors randomly assigned nondepressed patients at least 3 months poststroke to receive nortriptyline, fluoxetine, or placebo for 3 months using double-blind methodology. Patients were followed at 3, 6, 9, and 21 months for new onset of depression. In patients treated with antidepressants, lesion volume and degree of social impairment were associated with subsequent late-onset of poststroke depression at 6 and 9 months. In the placebo group, severity of impairment in activities of daily living, at 3 and 9 months, was associated with late onset poststroke depression. Differences in the clinical/pathological correlates may reflect subtle differences in the pathophysiology of poststroke depression following prophylactic antidepressants.     

Two-year longitudinal study of post-stroke mood disorders: dynamic changes in correlates of depression at one and two years

As part of a prospective study of 103 stroke patients, we have analyzed the relation between depression and associated variables at 3 months, 6 months, 1 year, and 2 years after stroke. At all intervals up to and including 1 year poststroke, patients with left hemisphere strokes showed a strong relation between severity of depression and distance of the lesion on computed tomography scan from the frontal pole. At 2 years poststroke, this relation was no longer significant. The correlation between depression and impairment in activities of daily living peaked at 6 months and thereafter fell but remained significant at 1 and 2 years poststroke. The correlation between depression and cognitive impairment and between depression and social functioning fluctuated--with most correlations at 1 and 2 years follow-up nonsignificant. Although the conclusions that can be drawn from this study are limited by the fact that less than half of the original patients were followed up at each time, these declining correlations between depression and associated variables at 1 and 2 years follow-up may reflect the natural course of major depression which spontaneously remits between 1 and 2 years after stroke. The persisting significant association of impairment in activities of daily living with depression may reflect the effect of severe depression in sustaining and possibly retarding recovery from physical impairment.     

A two-year longitudinal study of post-stroke mood disorders: dynamic changes in associated variables over the first six months of follow-up

We are prospectively studying a group of 103 stroke patients over the first 2 years after infarction to determine the variables which are associated with the development of depression. At both 3 and 6 months post-stroke, patients with left hemisphere infarcts showed a strong relationship between severity of depression and distance of the lesion on CT scan from the frontal pole. The strength of this association was unchanged from the immediate post-infarction period. In contrast, the correlation between degree of functional physical impairment and severity of depression steadily increased over the 6 month follow-up. The correlation between severity of depression and Mini-Mental score or between depression and social functioning score dropped between in-hospital and 3 months but then increased significantly between 3 and 6 months post-stroke. Age did not correlate with depression beyond the acute post-stroke period. Whether the increasing strength of the relationships between impairment and depression over the first 6 months post-stroke indicates that continued depression led to delayed recovery or whether continued severe impairments led to depression is not known, however, this issue will be addressed in further data evaluation from this prospective study.     

The effect of early versus late antidepressant treatment on physical impairment associated with poststroke depression: is there a time-related therapeutic window?

Impairments in activities of daily living (ADL) are common after stroke and may be related to poststroke depression. We have demonstrated that remission of poststroke major depression was associated with improvement in ADL. The administration of antidepressants within the first 3 months after stroke has been shown to prevent poststroke depression, early administration might also improve recovery of ADL among patients with stroke. This study examines the effect of early versus late treatment with antidepressants on recovery in ADL. Among 62 patients after stroke, the therapeutic effect of a 3-month course of antidepressants begun during the first month after stroke was compared with the effect of treatment begun after 1 month. The severity of impairment was measured using the Functional Independence Measure (FIM) and post-treatment outcome was assessed over the following 21 months. Although both the early and late treatment groups showed improvements in FIM scores during the 3 months of treatment, the early treatment group improved significantly more than the late treatment group. After the treatment, the early treatment group maintained this improvement over 2 years while the late treatment group deteriorated over time. There were no significant differences in the 2 groups that would explain the findings. Recovery in ADL impairment after stroke appeared to be enhanced by the use of antidepressant medication if treatment was started within the first month after stroke. These findings are consistent with the hypothesis that there may be a time-related therapeutic window in the treatment of physical impairment associated with poststroke depression.     

Does Cognitive Impairment Cause Poststroke Depression?

Studies have demonstrated that poststroke depression is associated with cognitive impairment, but have failed to show improvement in cognitive function when mood improves. A consecutive series of patients with (n=41) or without (n=135) major depression were evaluated for cognitive functioning during acute hospitalization and either 3 or 6 months later. Patients with poststroke major depression whose mood improved at follow-up had significantly greater recovery in cognitive functioning than patients whose mood did not improve. Furthermore, patients whose cognitive functioning improved at follow-up had significantly greater improvement in mood than comparable patients whose cognitive function did not improve, suggesting that poststroke major depression leads to cognitive impairment and not vice versa. The failure of previous treatment studies to show cognitive improvement in poststroke patients with depression was probably due to the inclusion of patients with minor depression (not associated with cognitive impairment) or the failure of patients with major depression to respond to treatment.     

Mortality and poststroke depression: a placebo-controlled trial of antidepressants

OBJECTIVE: Poststroke depression has been shown to increase mortality for more than 5 years after the stroke. The authors assessed whether antidepressant treatment would reduce poststroke mortality over 9 years of follow-up. METHOD: A total of 104 patients were randomly assigned to receive a 12-week double-blind course of nortriptyline, fluoxetine, or placebo early in the recovery period after a stroke. Mortality data were obtained for all 104 patients 9 years after initiation of the study. Demographic and clinical measurements were collected at 3, 6, 9, 12, 18, and 24 months after the stroke. Survival data were analyzed by using the Kaplan-Meier method. RESULTS: Of the 104 patients, 50 (48.1%) had died by the time of the 9-year follow-up. Of 53 patients who were given full-dose antidepressants, 36 (67.9%) were alive at follow-up, compared with only 10 (35.7%) of 28 placebo-treated patients, a significant difference. Logistic regression analysis showed that the beneficial effect of antidepressants remained significant both in patients who were depressed and in those who were nondepressed at enrollment, after the effects of other factors associated with mortality (i.e., age, coexisting diabetes mellitus, and chronic relapsing depression) were controlled. There were no intergroup differences in severity of stroke, impairment in cognitive functioning and activities of daily living impairment, and other medications received. CONCLUSIONS: Treatment with fluoxetine or nortriptyline for 12 weeks during the first 6 months poststroke significantly increased the survival of both depressed and nondepressed patients. This finding suggests that the pathophysiological processes determining the increased mortality risk associated with poststroke depression last longer than the depression itself and can be modified by antidepressants.     

Does cognitive recovery after treatment of poststroke depression last? A 2-year follow-up of cognitive function associated with poststroke depression

OBJECTIVE: Cognitive impairment is common after stroke and may be caused by poststroke depression. Remission of poststroke major depression after treatment has been associated with improvement in cognitive function. The current study was designed to examine how long that cognitive improvement lasts and to compare depressed patients' cognitive status with that of nondepressed patients with comparable lesions. METHOD: Seventeen patients with poststroke depression and cognitive impairment who had early and sustained remission of their depression during a double-blind treatment study were compared with 42 nondepressed stroke patients who remained nondepressed throughout the follow-up. Mood and cognitive function were followed-up over 2 years with the Hamilton Depression Rating Scale and Mini-Mental State Examination (MMSE). RESULTS: In the patients with early and sustained remission of depression, there was rapid improvement of cognitive function, which was maintained over 2 years. Their initial MMSE score of 23.3 (SD=4.2) improved to 26.6 (SD=3.5) at 3 months and was 26.1 (SD=3.6) at 2 years. The nondepressed patients showed essentially no change in cognitive function over 2 years (initial MMSE score: mean=26.3, SD=3.1; score at 2-year follow-up: mean=25.7, SD=4.1). CONCLUSIONS: Cognitive function, once improved after remission of poststroke depression, is likely to remain stable over the next 2 years in the absence of subsequent reinjury to the central nervous system. Cognitive impairment due to poststroke depression is reversible and can be quantified separately from cognitive impairment on the basis of the location and extent of ischemic brain damage.     

Phenomenological characteristics of poststroke depression: early- versus late-onset.

OBJECTIVE: Authors compared poststroke major (n=17) or minor (n=28) depression diagnosed 3 to 6 months poststroke with major (n=16) or minor (n=22) depression diagnosed at 12 to 24 months to identify changes in the phenomenological characteristics of poststroke depression over time. METHODS: Depressive symptoms were divided into vegetative, psychological symptoms, and melancholic features elicited by the Present State Exam (PSE). Patients were also examined for severity of depression, social impairment, and neurological findings. RESULTS: Early-onset poststroke major depression was associated with a higher frequency of vegetative symptoms and larger lesion volume than late-onset major depression. Similarly, early-onset minor depression was associated with poorer social functioning and a higher frequency of melancholic, vegetative, and psychological symptoms than late-onset minor depression. CONCLUSION: These findings suggest that the phenomenological characteristics of both major and minor poststroke depression change over time and that both early-onset major and minor poststroke depression may result from similar etiological mechanisms provoked by brain injury.     

Two-year longitudinal study of post-stroke mood disorders: comparison of acute-onset with delayed-onset depression

Patients who developed post-stroke depression 3 to 24 months after hospital discharge (N = 21) were compared with patients who developed depression during hospitalization (N = 26) and patients who never developed depression over 24 months of follow-up (N = 15). During the acute hospitalization and at follow-up, the three groups were not significantly different in their demographic characteristics, neurological impairment, intellectual impairment, or quality of social support. The acute depression group, however, showed an increased correlation between impairment and depression from hospitalization to follow-up. Findings suggest that impairment does not produce depression, but, once depression occurs, it may interact with impairment to influence post-stroke recovery.     

高血压脑出血卒中后抑郁风险因素相关性研究

目的 探讨高血压脑出血患者卒中后抑郁相关影响因素。方法 前瞻性录入65例急性高血压脑出血患者临床和计算机断层扫描（computer tomography,CT）影像资料,评估患者发病14d和3个月卒中后抑郁发生情况及生存质量状况,对临床资料和CT影像特征与卒中后抑郁的关系进行单因素和多因素分析。结果 65例患者中有57例完成14d随访,53例完成3个月随访。脑出血发病14d和3个月卒中后抑郁的发生率分别为35.1%和38.9％。单因素分析显示入院后首次美国国立卫生研究院卒中量表评分（thenational institutes of health stroke scale, NIHSS）与高血压脑出血发病后14d卒中后抑郁相关（P =0.027）。性别、出血部位和出血量与脑出血发病后3个月卒中后抑郁相关：与非抑郁组比较,抑郁组患者男性比例较低（P =0.038）,基底节出血比例较高（P =0.031）,平均出血量大（P =0.046）。多因素分析显示出血量是高血压脑出血患者发病3个月卒中后抑郁的风险预测因素（P =0.049）。结论 NIHSS评分和CT影像特征可作为高血压脑出血卒中后抑郁的评价指标,将CT影像与神经功能缺损程度评分有机结合可为脑出血综合性治疗策略的建立提供客观依据。     

Severity of aphasia and recovery after treatment in patients with stroke

Background: Aphasia due to stroke is often very severe immediately after onset. However, knowledge about the impact of severity on therapeutic potential in the first months is scarce. The optimal therapeutic approach for patients with severe aphasia is still subject to debate.

Aims: To explore the recovery pattern of verbal communication in stroke patients with aphasia of varying degrees of severity receiving language therapy during the first 6 months poststroke.

Methods & Procedures: We used data from our previous trial in which 80 patients with aphasia due to stroke were randomised within the first 3 weeks postonset for either cognitive-linguistic therapy (CLT) or communicative therapy. All patients were tested at baseline and at 3 and 6 months postaphasia onset. We formed three severity groups, based on baseline Amsterdam–Nijmegen Everyday Language Test scores. We used repeated measures ANOVA to compare test scores at baseline and at 3 and 6 months poststroke onset for each of the three severity groups, stratified for the two treatments.

Outcomes & Results: Patients with severe or very severe aphasia improved substantially during follow-up, especially during the first 3 months poststroke. Improvement was less pronounced in the moderate to mild group. Although improvement did not differ significantly between the two treatment arms of the trial during the first 6 months poststroke, the very severe group seemed to benefit particularly from CLT (mean difference between treatments was 4.1 points; 95% CI: ?4.0 to 12.2).

Conclusions: Even in very severely aphasic patients, considerable improvement of functional communication is possible. These patients might benefit more from early initiated CLT therapy than generally assumed. Hence, speech and language therapists should not refrain from applying CLT in the acute phase of rehabilitation of severe aphasia.     

Methylphenidate in treating poststroke depression

The authors retrospectively studied the charts of 25 patients with poststroke depression who were treated with methylphenidate. The 13 patients (52%) who recovered completely from their depression did not differ significantly from the 12 nonresponders on demographic characteristics, location of cerebrovascular accident, and other variables. Mood usually improved within 48 hours; only 3 (12%) patients had side effects. Rapid response to treatment and lack of significant side effects indicate that methylphenidate may be a valuable treatment for poststroke depression.     

Fatigue after stroke: a major but neglected issue

Subjective fatigue, defined as a feeling of early exhaustion developing during mental activity, with weariness, lack of energy and aversion to effort, remains virtually unstudied in patients with stroke, bur recent surveys suggest that it is a major, commonly overlooked, stroke sequela. While the few existing series did not show significant correlations between fatigue and stroke severity, lesion location, cognitive and neurological impairment and depression, recent neurobehavioral studies have highlighted an association between fatigue and brainstem and thalamic lesions. This suggests that fatigue may be linked to the interruption of neural networks involved in tonic attention, such as the reticular activating system. In fact, several subtypes of fatigue may develop after stroke, in connection with cognitive sequelae, neurological impairment, psychological factors and sleep disorders. A challenge is to identify and delineate these different subtypes and to distinguish them from mood disorders, which frequently coexist. We emphasize the concept of 'primary' poststroke fatigue, which may develop in the absence of depression or a significant cognitive sequela, and which may be linked to attentional deficits resulting from specific damage to the reticular formation and related structures involved in the subcortical attentional network. In the patients with excellent neurological and neuropsychological recovery, poststroke fatigue may be the only persisting sequela, which may severely limit their return to previous activities. The recognition of poststroke fatigue may be critical during recovery and rehabilitation after stroke.     

Poststroke depression in acute phase after stroke.

We studied factors associated with acute poststroke depression in 100 patients, aged 27-70, 2 weeks after their first clinically significant stroke. Depressive symptoms were relatively common (27% Beck Depression Inventory > or =10), but the prevalence of major depression was only 5.6%. Older patients were most vulnerable to poststroke depression. Patients with left hemisphere lesion had no more depression than other patients, but when the lesion was in the left hemisphere or in the brainstem, stroke severity was associated with depression.     

Rates of depression at 3 and 15 months poststroke and their relationship with cognitive decline: the Sydney Stroke Study.

OBJECTIVE: To investigate the frequency and correlates of depression at 3 and 15 months after stroke. METHODS: A total of 164 consecutive eligible stroke patients and 100 comparison subjects received extensive medical, psychiatric, and neuropsychological assessments; a subset also received magnetic resonance imaging scans. Comprehensive assessments included ratings for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition major or minor depression at 3-6 months (index assessment) and 15 months (follow-up assessment) after stroke. The comparison subjects, who were similar in age and sex, were similarly assessed twice, 12 months apart. RESULTS: Major or minor depression was present in 12.0% of stroke patients at index assessment and in 20.7% at follow-up which included 18 new cases (13.4%). By follow-up, stroke patients with depression had significantly greater impairment of functional ability and global cognition than nondepressed stroke patients or comparison subjects. Depression was not associated with age, intellectual decline prior to stroke or side or severity of stroke. Patients who experienced a TIA or stroke during the follow-up, who had developed dementia by three months or who were not living with a relative or partner were more likely to be depressed at follow-up. Dementia at 3 months predicted depression, but the reverse did not hold. CONCLUSION: Depression may be less frequent after stroke than previously reported and is related to cumulative vascular brain pathology rather than side and severity of single strokes. Clinicians should strive to slow the progression of cerebrovascular disease and encourage greater social support.     

Is fatigue an independent factor associated with activities of daily living, instrumental activities of daily living and health-related quality of life in chronic stroke?

BACKGROUND: To determine the longitudinal association of poststroke fatigue with activities of daily living (ADL), instrumental ADL (IADL) and perceived health-related quality of life (HRQoL) and to establish whether this relationship is confounded by other determinants. METHODS: A prospective cohort study of stroke patients consecutively admitted for inpatient rehabilitation was conducted. ADL, IADL and HRQoL were assessed in 223 patients at 6, 12 and 36 months after stroke. Fatigue was determined by the Fatigue Severity Scale. Random coefficient analysis was used to analyze the impact of fatigue on ADL, IADL and HRQoL. The association between fatigue and outcome was corrected for potential confounders, i.e. age, gender, comorbidity, executive function, severity of paresis and depression. The covariate was considered to be a confounder if the regression coefficient of fatigue on outcome changed by >15%. RESULTS: Fatigue was significantly related to IADL and HRQoL but not to ADL. The relation between fatigue and IADL was confounded by depression and motor impairment. Depression biased the relation between fatigue and HRQoL, but fatigue remained independently related to HRQoL. CONCLUSIONS: Fatigue is longitudinally spuriously associated with IADL and independently with HRQoL. These findings suggest that in examining the impact of poststroke fatigue on outcome, one should control for confounders such as depression.     

Treatment of poststroke generalized anxiety disorder comorbid with poststroke depression: merged analysis of nortriptyline trials.

OBJECTIVE: The existence of anxiety disorders plays an important role in the prognosis and associated impairment among patients with poststroke depression. The authors examined the efficacy of nortriptyline treatment for patients with comorbid generalized anxiety disorder (GAD) and depression after stroke. METHODS: Data from three studies were merged to provide 27 patients with comorbid GAD and depression, who participated in double-blind treatment studies comparing nortriptyline (N=13) and placebo (N=14). Severity of anxiety was measured with the Hamilton Rating Scale for Anxiety (Ham-A), and severity of depression was measured with the Hamilton Rating Scale for Depression (Ham-D). Activities of daily living were assessed by use of the Johns Hopkins Functioning Inventory (JHFI). RESULTS: There were no significant differences between the nortriptyline and placebo groups in demographic characteristics, stroke type, and neurological findings. Patients receiving nortriptyline treatment showed significantly greater improvement on the Ham-A, Ham-D, and JHFI than patients receiving placebo. The anxiety symptoms showed earlier improvement than depressive symptoms in patients treated with nortriptyline. CONCLUSIONS: These findings suggest that poststroke GAD comorbid with poststroke depression may be effectively treated with nortriptyline, and data indicate the need for a trial specifically designed to examine treatment of anxiety disorder.     

William Feinberg lecture 2002: emotions,mood, and behavior after stroke

While emotional outcome is a critical factor influencing early evolution and late prognosis after stroke, few relevant studies have been performed on this subject. However, mood changes, modified judgment, and emotional reactions may also dramatically alter recruitment into clinical trials; for instance, up to one third of patients with acute stroke may have altered time perception, inappropriate self-evaluation of their condition, and attentional or memory dysfunction, with a subsequent increase in referral-to-hospital delays. In addition, the value of the "informed" consenting process may be questionable in the setting of urgent randomization into an acute stroke clinical trial. Data from ongoing studies suggest that behavior and emotional reactions in acute stroke patients may be classified into a few broad categories, with considerable overlap. Correlations between mood changes and the type, location, and severity of stroke may provide useful information for improving patient management, including the prediction of functional evolution and late prognosis. While depressive reactions have been widely studied in the recovery-rehabilitation phase after stroke, significant depression is uncommon shortly after stroke. On the other hand, related, though different, emotional behavioral changes may be more frequent; these have often been confused with depression and include catastrophic reaction, emotionalism, and athymhormia. Late depression is the most common mood alteration during the first year after stroke and has specific characteristics that differentiate it from classic endogenous and reactive depression, thus emphasizing the critical role of brain damage in the pathogenesis of poststroke depression. Early recognition and management of mood disorders after stroke are critical for the functional improvement of individual patients. However, little is known about specific indications for different antidepressant drugs in poststroke depression and related disorders. Ongoing research has identified a "new" emotional-behavioral disorder, poststroke fatigue, which is clearly distinct from depression in most instances. It is especially disabling and frustrating in that it typically involves patients with total or near-total neurological recovery, who should have been able to go back to their previous activities but who become severely disabled because of early and persisting exhaustion. Preliminary neuropsychological and MR and PET imaging studies suggest that disruption of subtle mechanisms underlying attention, in the absence of significant cognitive and mood alterations, may be responsible. Research projects are now being launched to better delineate poststroke fatigue and its management.     

Dimensions of social impairment and their effect on depression and recovery following stroke

Prior studies have identified that quality of social functioning is strongly associated with both physical and cognitive recovery from stroke as well as with the existence of depression. This study was undertaken to identify the specific elements of social functioning that are related to depression and impaired recovery and to determine whether these elements are different between acute and chronic periods following stroke. There were 50 patients with acute stroke who were assessed in the hospital and at short-term (3- or 6-month) and long-term (12- or 24-month) follow-up. An impaired relationship with the patient's "closest other" prior to the stroke and limited social activities were both associated with depression immediately after the stroke as well as with depression at long-term follow-up. An impaired relationship with the closest other prior to the stroke was also associated with impaired recovery in activities of daily living and cognitive recovery at long-term follow-up. Fears of economic stability and limited social activity were associated with depression at short-term follow-up whereas loss of job or job satisfaction was associated with depression at long-term follow-up. These findings suggest that during the first few weeks following stroke, social supports and contact are essential needs for patients, whereas during the chronic period, other factors such as financial security, adequacy of living arrangements, and loss of job satisfaction also become important. Future research should examine the effect of enhanced social support on poststroke depression and physical and cognitive recovery.