The role of objective cognitive dysfunction in subjective cognitive complaints after stroke.

BACKGROUND AND PURPOSE: Objective cognitive performance (OCP) is often impaired in patients post-stroke but the consequences of OCP for patient-reported subjective cognitive complaints (SCC) are poorly understood. We performed a detailed analysis on the association between post-stroke OCP and SCC. METHODS: Assessments of OCP and SCC were obtained in 208 patients 3 months after stroke. OCP was evaluated using conventional and ecologically valid neuropsychological tests. Levels of SCC were measured using the CheckList for Cognitive and Emotional (CLCE) consequences following stroke inventory. Multivariate hierarchical regression analyses were used to evaluate the association of OCP with CLCE scores adjusting for age, sex and intelligence quotient. Analyses were performed to examine the global extent of OCP dysfunction (based on the total number of impaired neuropsychological tests, i.e. objective cognitive impairment index) and for each OCP test separately using the raw neuropsychological (sub)test scores. RESULTS: The objective cognitive impairment index for global OCP was positively correlated with the CLCE score (Spearman's rho = 0.22, P = 0.003), which remained significant in multivariate adjusted models (ß = 0.25, P = 0.01). Results for the separate neuropsychological tests indicated that only one task (the ecologically valid Rivermead Behavioural Memory Test) was independently associated with the CLCE in multivariate adjusted models (ß = -0.34, P < 0.001). CONCLUSIONS: Objective neuropsychological test performance, as measured by the global dysfunction index or an ecologically valid memory task, was associated with SCC. These data suggest that cumulative deficits in multiple cognitive domains contribute to subjectively experienced poor cognitive abilities in daily life in patients post-stroke.

An early prediction of delirium in the acute phase after stroke.

BACKGROUND: We developed and validated a risk score to predict delirium after stroke which was derived from our prospective cohort study where several risk factors were identified. METHODS: Using the ß coefficients from the logistic regression model, we allocated a score to values of the risk factors. In the first model, stroke severity, stroke subtype, infection, stroke localisation, pre-existent cognitive decline and age were included. The second model included age, stroke severity, stroke subtype and infection. A third model only included age and stroke severity. The risk score was validated in an independent dataset. RESULTS: The area under the curve (AUC) of the first model was 0.85 (sensitivity 86%, specificity 74%). In the second model, the AUC was 0.84 (sensitivity 80%, specificity 75%). The third model had an AUC of 0.80 (sensitivity 79%, specificity 73%). In the validation set, model 1 had an AUC of 0.83 (sensitivity 78%, specificity 77%). The second had an AUC of 0.83 (sensitivity 76%, specificity 81%). The third model gave an AUC of 0.82 (sensitivity of 73%, specificity 75%). We conclude that model 2 is easy to use in clinical practice and slightly better than model 3 and, therefore, was used to create risk tables to use as a tool in clinical practice. CONCLUSIONS: A model including age, stroke severity, stroke subtype and infection can be used to identify patients who have a high risk to develop delirium in the early phase of stroke.

Delirium in the acute phase after stroke and the role of the apolipoprotein E gene.

OBJECTIVE: To study the association between the epsilon 4 allele of apolipoprotein E (APOEε4) and delirium in a stroke population. METHODS: 527 consecutive stroke patients were screened for delirium during the first week of admission with the confusion assessment method. In three hundred fifty-three patients genomic DNA isolation was available. RESULTS: The incidence of delirium after stroke in the 353 patients was 11.3%. There was no association between APOEε4 and delirium. Even after adjustment for IQCODE, stroke localization, stroke subtype, stroke severity, infection, and brain atrophy no association was found (odds ratio: 0.9; 95% confidence interval: 0.4-2.1). Delirium did not last longer in patients with an APOEε4 allele compared to patients without an APOEε4 allele (median: 5.6 days [range: 1-21] versus median: 4.6 days [range: 1-15], p = 0.5). CONCLUSION: There was no association between the presence of an APOEε4 allele and the occurrence of delirium in the acute phase after stroke.

Delirium in the acute phase after stroke: incidence, risk factors, and outcome.

OBJECTIVES: This prospective cohort study assesses incidence of delirium after stroke. In addition, risk factors during the first week were assessed. Finally, outcome in relation to development of delirium was studied. METHODS: A total of 527 consecutive patients with stroke (median age, 72 years; range, 29-96 years) were screened for delirium during the first week after admission. We diagnosed delirium with the Confusion Assessment Method. Cognitive functioning prior to the stroke was assessed with the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Neurologic deficits were assessed with the NIH Stroke Scale. RESULTS: A total of 62 patients with stroke (11.8%) developed delirium during the first week of admission. Independent risk factors were preexisting cognitive decline (odds ratio [OR] for IQCODE above 50: 2.6, 95% confidence interval [CI] 1.2-5.7) and infection (OR 3.4, 95% CI 1.7-6.8). Furthermore, right-sided hemispheric stroke (OR 2.0, 95% CI 1.0-3.0), anterior circulation large-vessel stroke (OR 3.4, 95% CI 1.1-10.2), the highest tertile of the NIH Stroke Scale (OR for highest vs lowest tertile 15.1, 95% CI 3.3-69.0), and brain atrophy (OR for highest versus lowest tertile 2.7, 95% CI 1.1-6.8) increased the risk for delirium. Delirium was associated with a worse outcome in terms of duration of hospitalization, mortality, and functional outcome. CONCLUSIONS: Delirium occurs in almost 1 out of every 8 patients with stroke on a stroke unit and is associated with cognitive decline, infection, right-sided hemispheric stroke, anterior circulation large-vessel stroke, stroke severity, and brain atrophy. Delirium after stroke is associated with a worse outcome.

The reliability and validity of the PALOC-s: a post-acute level of consciousness scale for assessment of young patients with prolonged disturbed consciousness after brain injury.

The objective of the study was the validation of the Post-Acute Level of Consciousness scale (PALOC-s) for use in assessing levels of consciousness of severe brain injured patients in a vegetative state or in a minimally conscious state. A cohort of 44 successively admitted patients (between 2 and 25 years of age), who were treated in an early intensive neurorehabilitation programme, were included in the study. Each patient was examined, using the Western Neuro Sensory Stimulation Profile (WNSSP) and the Disability Rating Scale (DRS), once every two weeks resulting in 327 examinations (all videotaped). To determine the reliability of the PALOC-s, six observers rated one videotape of each patient. One of the observers rated the same tapes a second time, 3-4 months later. Validity was determined by correlating 100 ratings of one observer with the scores on the WNSSP and the DRS. To determine the responsiveness of the PALOC-s, the size of change between the scores of the first and last examinations was calculated. The inter-observer correlations and agreement scores varied between .82 and .95. The intra-observer correlation and agreement scores varied between .94 and .96. Correlations with the WNSSP varied between .88 and .93, and with the DRS between .75 and .88. The responsiveness was significantly high (t=8.2), with a standardised effect size of 1.30. It is concluded that the PALOC-s is a reliable, valid, and responsive observation instrument provided it is administered after a structured assessment by an experienced and trained clinician. The PALOC-s is feasible for use in clinical management, as well as in outcome research.

Acute neglect rehabilitation using repetitive prism adaptation: a randomized placebo-controlled trial.

PURPOSE: At present, prism adaptation is probably the most promising rehabilitation procedure for hemi-neglect. However, randomised controlled trials are lacking and no data are available on the effectiveness of prism adaptation in the treatment of acute neglect. METHODS: We followed sixteen neglect patients using a randomised controlled design in which six patients received four-day-in-a-row placebo treatment (CG) and ten patients received four-day-in-a row experimental treatment with 10 degrees rightward deviating prisms (EG) during their stay on the stroke unit. We examined whether patients in the EG improved faster than the CG by administering three neglect tasks (Schenkenberg Line Bisection, Letter Cancellation, Gainotti Scene Copying) immediately before and after each treatment. Second, we examined whether patients in the EG demonstrated a better long-term outcome at one month post-treatment (Behavioural Inattention Test). RESULTS: Patients in the EG improved faster on spatial tasks (line bisection, cancellation) than the CG but not on visuo-construction. Patients in the EG showed no differences with the CG in neglect outcome at one month post-treatment. CONCLUSIONS: Four consecutive prism sessions produced beneficial effects in patients with acute neglect. However, prism effects were either short-term, or placebo treatment with repeated pointing and/or repeated neglect testing was more helpful than we anticipated. Our results emphasize the importance of a placebo condition and a follow-up in rehabilitation studies.

[Multiple emboli from a cardiac metastasis of a renal-cell carcinoma]. / Multipele embolieën veroorzaakt door een cardiale metastase van een niercelcarcinoom.

A 68-year-old man was hospitalised with a vascular occlusion in the left leg. After treatment with urokinase he developed multiple intracerebral haemorrhages. The occlusion and the intracerebral haemorrhages evoked by urokinase were caused by embolisation originating from a cardiac metastasis of a renal-cell carcinoma. Cardiac surgery was performed, but complete removal of the tumour was not possible. The process of embolisation continued and the patient died a few weeks after diagnosis. Cardiac metastasis is seen in 10% of all cancer patients. Most of these metastases remain without symptoms. Left ventricular metastasis of renal-cell carcinoma without involvement of the inferior V. cava is very rare. If embolic occlusion of one or more vascular areas is present, transthoracic echography of the heart should be performed. Early detection and surgical treatment prevent further embolisation which may result in a better prognosis.

Cognitive disorders in acute stroke: prevalence and clinical determinants.

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.

Children and young adults in a prolonged unconscious state after severe brain injury: long-term functional outcome as measured by the DRS and the GOSE after early intensive neurorehabilitation.

OBJECTIVE: To investigate the long-term (2-15 years) functional outcome of children and young adults who received an early intensive neurorehabilitation programme (EINP) after a prolonged period of unconsciousness due to severe brain injury; to differentiate between traumatic brain injury (TBI) and non-traumatic brain injury (nTBI); and to compare the results on two different outcome scales: the Disability Rating Scale (DRS) and the Glasgow Outcome Scale Extended (GOSE). SUBJECTS: One hundred and forty-five patients, who were admitted to EINP between December 1987 and January 2001. OUTCOME MEASURES: The Post-Acute Level of Consciousness scale (PALOC-s), the DRS, including categorized scores (DRScat), and the GOSE. RESULTS: The long-term functional level of 90 patients could be determined, of whom 25 were deceased. The mean DRS-score of the surviving patients was 6.8 (SD = 6.6); the mean score on the GOSE was 4.5 (SD = 1.7). There was a significant difference in the outcome amongst traumatic and non-traumatic patients (t88 = 4.21; p < 0.01). The correlation between the DRS and the GOSE was high (Spearman rho = 0.85; p < 0.01), as well as the correlation between the categorized scores of the DRS and the GOSE (Spearman rho = 0.81; p < 0.01). The distribution of outcome scores on the DRScat is more diverse than on the GOSE. Especially item 7 of the DRS, measuring functional independence, showed considerable variance in discriminating between different outcome levels. CONCLUSIONS: More patients with TBI than expected reached a (semi-) independent level of functioning, indicating a possible effect of EINP. Patients suffering from nTBI did not demonstrate these outcome levels. Only a few patients stayed in a vegetative state for more than a couple of years. In this cohort of severe brain-injured young people, the DRS offered the best investigative possibilities for long-term level of functioning.

Delirium in acute stroke: a review.

BACKGROUND: Delirium is a complex neuropsychiatric syndrome characterized by disturbances of consciousness, attention, cognition, and perception. It may be the presenting feature of acute stroke, but more often it complicates the clinical course in the early stage of rehabilitation. SUMMARY OF REVIEW: Risk factors for delirium are older age, pre-existing cognitive decline, metabolic disturbances, infections, and polypharmacy. Recognition of delirium in patients with stroke is important because of its association with a longer stay in the hospital, a poor functional outcome, and an increased risk of developing dementia. The diagnosis may be difficult because of the fluctuating course and the neurological deficits that are caused by the stroke. Nonpharmacological preventive measures, early identification, and additional medical intervention are the key measures in the management of delirium after stroke. CONCLUSION: This review describes incidence, risk factors, pathophysiology, diagnostic tools, and management of delirium in patients with a recent stroke.

Early cognitive impairment predicts long-term depressive symptoms and quality of life after stroke.

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.

[Cerebral infarction after cocaine use]. / Herseninfarct na cocaïnegebruik.

Three relatively young patients, men aged 29 and 38 years and a woman aged 40 years, developed ischaemic stroke shortly after cocaine use. All three had used cigarettes or alcohol as well, and suffered from neurologic deficits with CT and MRI lesions. They recovered, but neurologic sequelae remained. Cocaine may induce haemorrhagic as well as ischaemic stroke. Different vascular complications of cocaine may be involved. The pathophysiologic mechanisms of cocaine-induced ischaemic stroke include vasoconstriction due to cerebrovascular spasms and serotoninergic action, and enhanced thrombocyte aggregation. Over the last years, the use of cocaine is rising, so that the number of cocaine-related stroke patients can be expected to increase. Cocaine use as a cause of ischaemic stroke is important to recognise because discontinuation of cocaine can prevent a recurrent stroke.

Children and young adults in a prolonged unconscious state due to severe brain injury: outcome after an early intensive neurorehabilitation programme.

PRIMARY OBJECTIVE: The Rehabilitation Centre Leijpark in The Netherlands provides an Early Intensive Neurorehabilitation Programme (EINP) to children and young adults in a prolonged unconscious state after severe brain injury. In an extensive research project the effects of EINP were studied. This part of the project focused on the outcome in terms of level of consciousness (LOC) in relation to the specific characteristics of a retrospectively studied cohort. RESEARCH DESIGN: This study was executed according to a one-group archived pre-test-post-test design. SUBJECTS: Subjects were all consecutively admitted patients (n=145, 72% male) between December 1987-January 2001. Inclusion criteria were: age 0-25 years, within 6 months after injury, LOC at admission vegetative state (VS) or minimally conscious state (MCS). One hundred and four patients (72%) suffered a traumatic injury and 41 patients (28%) a non-traumatic injury. METHODS AND PROCEDURES: All patients had received EINP until they reached consciousness or until it was concluded that no progress was achieved during 3 months after the start of EINP. Medical files were investigated to collect the patients' characteristics and injury data, to determine the LOC at admission and at discharge and to determine the discharge destination. RESULTS: Almost two-thirds of the patients reached full consciousness. LOC at admission, aetiology and interval since injury were found to be significant prognostic factors. Traumatic patients had a much better outcome than non-traumatic patients. A comparison with earlier outcome studies showed a more favourable outcome than expected. It is argued that a multi-centre study is needed to confirm possible effects of EINP.

Restrictions of the Mini-Mental State Examination in acute stroke.

While the Mini-Mental State Examination (MMSE) was originally developed to screen for dementia and delirium, many neurologists use this measure as a screening instrument for 'cognitive impairment' in hospitalized stroke patients. However, the validity of the MMSE as such has never been evaluated in acute stroke. We administered the MMSE in addition to a neuropsychological examination covering six cognitive domains to 34 stroke patients (mean interval between stroke and examination, 6.5+/-2.9 days) and 34 healthy controls. The area under the receiver operating characteristic curve (AUC) was calculated in addition to the sensitivity and specificity for various cut-off points on the MMSE. Seventy percent of the patients were impaired in at least one cognitive domain. The accuracy of the MMSE in detecting cognitive impairment was no better than chance (AUC = 0.67; p = 0.13). No optimum MMSE cut-off value could be identified. The MMSE is particularly insensitive to impairments in abstract reasoning, executive functioning, and visual perception/construction.

The prognostic value of domain-specific cognitive abilities in acute first-ever stroke.

OBJECTIVE: To evaluate the prognostic value of domain-specific cognitive abilities in acute stroke with respect to long-term cognitive and functional outcome in addition to neurologic and demographic predictors. METHODS: The authors evaluated 168 patients within the first 3 weeks after first-ever stroke. The prevalence of neuropsychological impairment was calculated vs 75 matched healthy controls. The authors also recorded demographic data, vascular risk factors, lesion characteristics, and clinical factors at admission. Independent predictor variables associated with long-term cognitive impairment (assessed with a follow-up neuropsychological examination) and functional impairment (assessed with the modified Barthel Index and the Frenchay Activities Index) were identified with stepwise multiple logistic regression. Areas under receiver operator characteristic curves were used to compare the predictive value of three models, i.e., a standard medical model, a purely cognitive model, and a model consisting of both medical and cognitive predictors. RESULTS: Thirty-one percent of patients showed long-term cognitive impairment. Basic and instrumental ADL disturbances remained present in 19% and 24% of patients. Domain-specific cognitive functioning predicted cognitive and functional outcome better than any other variable. Moreover, the prediction of instrumental ADL functioning improved when cognitive predictors were added to the standard medical model (p < 0.05). Impairments in abstract reasoning and executive functioning were independent predictors of long-term cognitive impairment. Inattention and perceptual disorders were more important in predicting long-term functional impairment. CONCLUSION: Domain-specific cognitive abilities in the early phase of stroke are excellent independent predictors of long-term cognitive and functional outcome.

Early depressive symptoms after stroke: neuropsychological correlates and lesion characteristics.

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.

Domain-specific cognitive recovery after first-ever stroke: a follow-up study of 111 cases.

The objective of this study is to examine the prognosis of acute cognitive disorders post-stroke, and to evaluate which clinical factors predict domain-specific cognitive recovery. We followed the course of cognitive functioning in 111 stroke patients and 77 healthy controls by administering two neuropsychological examinations with a 6 to 10 month interval (mean interval, 7.5 +/- 1.3 months). The baseline examination was administered within three weeks post-stroke (mean interval, 7.9 +/- 4.2 days). To examine determinants of domain-specific cognitive recovery, we recorded vascular risk factors, clinical variables, and lesion characteristics. Recovery in visual perception/construction (83%) and visual memory (78%) was the most common. An acute cognitive disorder predicted a long-term disorder in the same domain (all p < .05), except for visual perception/construction. Factors associated with poor cognitive recovery were age (all p < .01), preexistent verbal ability (all p < .005), lesion locations involving the temporal (all p < .05), frontal (p < .05) and occipital lobe (allp < .05), lesion volume (p < or = .001), and diabetes mellitus (p < .01). An early neuropsychological examination provides valuable information on long-term cognitive performance. The prognosis of higher-level visual disorders is the most favorable. Cognitive recovery is associated with age, preexistent ability, lesion volume, lesion location, and diabetes mellitus.

Difference in distribution of muscle weakness between myasthenia gravis and the Lambert-Eaton myasthenic syndrome.

BACKGROUND: Myasthenia gravis and the Lambert-Eaton myasthenic syndrome (LEMS) may have a similar distribution of muscle weakness. Deciding on a diagnosis of myasthenia gravis or LEMS on clinical grounds may therefore be difficult. OBJECTIVE: To compare the localisation of initial muscle weakness and the distribution of weakness at the time of maximum severity in patients with myasthenia gravis and LEMS. SUBJECTS: 101 patients with myasthenia gravis and 38 patients with LEMS. RESULTS: In myasthenia gravis, initial weakness involved extraocular muscles in 59%, bulbar muscles in 29%, and limb muscles in 12% of the patients. In LEMS no patient had ocular weakness, 5% had bulbar weakness, and 95% had weakness of the limbs as the first symptom (p < 0.001). At the point of maximum severity, weakness in myasthenia gravis was purely ocular in 25%, oculobulbar in 5%, restricted to the limbs in 2%, and present in both oculobulbar muscles and limbs in 68%. At this point, none of the LEMS patients had weakness restricted to extraocular or bulbar muscles (p = 0.002). The legs were affected in all LEMS patients, whereas in 12 patients with generalised myasthenia gravis limb weakness was restricted to the arms (p = 0.024). CONCLUSIONS: In a patient suspected to have a myasthenic syndrome whose first symptom is ocular weakness, LEMS is virtually excluded. Limb weakness confined to the arms is only found in generalised myasthenia gravis and not in LEMS. Muscle weakness in myasthenia gravis tends to develop in a craniocaudal direction, and in the opposite direction in LEMS.