Neglect and aphasia in the acute phase as predictors of functional outcome 7 years after ischemic stroke.

BACKGROUND AND PURPOSE: Visuospatial inattention (VSI) and language impairment (LI) are often present early after stroke and associations with an unfavorable short-term functional outcome have been reported. The purpose of this study was to investigate whether a screening of VSI and LI as indicators of cortical symptoms early after stroke could predict long-term functional outcomes. METHODS: A consecutive cohort of 375 patients with ischemic stroke was assessed for the occurrence of VSI at a median of 7 days after admission (interquartile range, 1-5 days) using the Star Cancellation Test and for LI (within the first 7 days) with the language item in the Scandinavian Stroke Scale. Seven years later, functional outcomes were assessed by the modified Rankin scale and Frenchay Activities Index in 235 survivors without recurrent stroke. Relationships between baseline predictors and functional outcome at 7 years were analyzed with bivariate correlations and multiple categorical regressions with optimal scaling. RESULTS: The regression model significantly explained variance in the modified Rankin scale (R2 = 0.435, P < 0.001) and identified VSI (P = 0.001) and neurological deficits (P < 0.001; Scandinavian Stroke Scale score without the language item) as the significant independent predictors. The model for Frenchay Activities Index was also significant (R2 = 0.269, P < 0.001) with VSI (P = 0.035) and neurological deficits (P < 0.001) as significant independent predictors. CONCLUSIONS: Visuospatial inattention at acute stroke has an independent impact on long-term functional outcomes. Early recognition may enable targeted rehabilitative interventions.

Daily life consequences, cognitive impairment, and fatigue after transient ischemic attack.

OBJECTIVES: Studies suggest that fatigue and cognitive impairment may be present after transient ischemic attack (TIA), but little is known about consequences in daily life. The main aim was to longitudinally explore the presence of fatigue, cognitive impairment, and consequences in daily life including communication after clinically diagnosed TIA at 1 and 9 months after the event. MATERIAL AND METHODS: A consecutive sample of 46 patients (23 women, 69 ± 12.3 years) was assessed at discharge from hospital and at 1 and 9 months after TIA regarding cognition, mental fatigue, tiredness, and activities of daily life. This served as basis for an interview concerning experienced changes related to the TIA. RESULTS: Problems in daily life with probable association with the TIA were experienced by 37% (n = 45) of participants 9 months after the TIA event. Cognitive impairment was present in 40% (n = 44) after 1 month and 30% (n = 23) after 9 months. Mental fatigue was experienced by 26% (n = 42) after 1 month and 17% (n = 39) after 9 months. Communication problems were reported and increased from 7 to 14 participants between the two time points. CONCLUSIONS: A third of the TIA patients experienced problems in performance of complex activities in daily life and often communication problems within the first 9 months. Cognitive impairment and mental fatigue could be factors influencing performance in daily life and at work, but this needs to be verified in a larger sample. The risk of activity limitations indicates need for multiprofessional support and systematic routines for TIA follow-up.

The prediction of functional dependency by lateralized and non-lateralized neglect in a large prospective stroke sample.

BACKGROUND AND PURPOSE: Lateralized and non-lateralized impairments in visual attention have been identified as important components in patients with visuospatial neglect. This study investigated the course of these two phenomena across time in relation to neurological symptoms and functional outcome in a large consecutive and prospective stroke sample. METHODS: A total of 375 consecutive stroke patients were divided into three groups (lateralized, non-lateralized or no visual inattention) acutely and 3 months post-stroke using the star cancellation test. Neurological impairments, localization of brain damage, asymmetry in clinical symptoms and functional outcome were assessed. Possible group differences were analysed, and stepwise logistic regressions were performed to examine the relative importance of predictors of functional dependency. RESULTS: Participants with acute lateralized inattention differed (P ≤ 0.05) from the other two groups by more often exhibiting severe neurological symptoms, functional dependency and persisting visual inattention. The regression analyses selected acute lateralized inattention as an important and independent predictor of functional dependency following right hemisphere damage, but not following left hemisphere damage. CONCLUSIONS: The results emphasize the prognostic value of lateralized inattention and the importance of separating lateralized and non-lateralized symptoms of visual inattention at the commencement of rehabilitation.

Stroke subtype predicts outcome in young and middle-aged stroke sufferers.

OBJECTIVES: There are few studies on long-term outcome after ischemic stroke (IS) for young and middle-aged stroke sufferers in relation to etiologic subtypes. Here, we report 2-year outcome in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). MATERIALS AND METHODS: SAHLSIS comprises 600 patients with IS before the age of 70 years. Etiologic subtype of IS was classified according to Trial of Org 10172 in Acute Stroke Treatment (TOAST). Recurrent vascular events and death were registered using several overlapping methods. Functional outcome was assessed according to the modified Rankin Scale (mRS). RESULTS: After 2 years, 55 (9.2%) patients had suffered a recurrent stroke, 15 (2.5%) had a transient ischemic attack (TIA), 4 (0.7%) had a coronary event, and 24 (4.0%) had died. The number of recurrent stroke, TIA, and death differed significantly between etiologic stroke subtypes. The highest rates were observed in large-vessel disease (LVD), whereas small-vessel disease and cryptogenic stroke showed the lowest recurrence and mortality rates. LVD was a significant predictor of the composite outcome (recurrent stroke, TIA, coronary event and/or death) independently of cardiovascular risk factors and stroke severity. Stroke subtype also predicted functional outcome 2 years after index stroke, but this association was not retained after adjustment for stroke severity. CONCLUSIONS: In young and middle-aged stroke patients, stroke subtype predicts recurrent vascular events and/or death 2 years after index stroke independently of cardiovascular risk factors and stroke severity. Thus, it is important to take the etiologic subtype of IS in account when assessing the risk of recurrence both in the clinical setting and in future studies.

Genetic variation on chromosome 9p21 shows association with the ischaemic stroke subtype large-vessel disease in a Swedish sample aged ≤ 70.

BACKGROUND: The aim of this study was to investigate whether we could replicate a recent finding of an association between genetic variants on chromosome 9p21 and the ischaemic stroke (IS) subtype large-vessel disease (LVD). METHODS: The Sahlgrenska Academy Study on Ischemic Stroke comprises 844 patients with IS, who suffered IS before reaching the age of 70, and 668 healthy controls. IS subtype was defined according to the TOAST criteria, and 111 patients were categorized as LVD. Seven single-nucleotide polymorphisms (SNPs) on 9p21 were analyzed. Functional outcome was assessed 3 months after IS using the modified Rankin scale. RESULTS: The SNP rs7857345 showed a significant association with the subtype LVD independent of traditional vascular risk factors. In addition, an association between rs7857345 and functional outcome after LVD was observed. CONCLUSION: In this relatively young sample of patients with IS, genetic variation on 9p21 is associated with LVD.

Genetic variation in complement component C3 shows association with ischaemic stroke.

BACKGROUND AND PURPOSE: The aim of this study was to investigate whether genetic variation at the third complement component (C3) locus is associated with ischaemic stroke (IS). METHODS: The Sahlgrenska Academy Study on Ischaemic Stroke comprises 844 patients with IS, and 668 healthy controls. Sixteen SNPs were analyzed. RESULTS: Two SNPs, rs2277984 and rs3745565, showed a significant association with overall IS. The SNP rs2277984 also showed association with the IS subtype cryptogenic stroke. These associations were independent of hypertension, diabetes, and smoking. The independent association between rs3745565 and overall IS withstands correction for multiple testing. CONCLUSION: In this sample of patients with IS, genetic variation in C3 is associated with IS.

Little evidence for different phenomenology in poststroke depression.

OBJECTIVE: It remains unclear whether mood depressive disorders after stroke have a distinct phenomenology. We evaluated the symptom profile of poststroke depression (PSD) and assessed whether somatic symptoms were reported disproportionately by stroke patients. METHOD: The sample was 149 stroke patients at 18 months poststroke and 745 age- and sex-matched general population controls. A comprehensive psychiatric interview was undertaken and depression was diagnosed according to DSM-III-R criteria. RESULTS: Depressed controls reported more 'inability to feel' (P = 0.002) and 'disturbed sleep' (P = 0.008) than depressed stroke patients. Factor analysis of the 10 depressive symptoms identified two main factors, which appeared to represent somatic and psychological symptoms. There was no difference in scores on these two factors between stroke patients and controls. CONCLUSION: Phenomenology of depression at 18 months poststroke is broadly similar but not the same as that described by controls. Somatic symptoms of depression were not over-reported by stroke patients.

Comparative studies on mitochondria isolated from neuron-enriched and glia-enriched fractions of rabbit and beef brain.

Fractions enriched in neuronal and glial cells were obtained from dispersions of whole beef brain and rabbit cerebral cortex by large-scale density gradient centrifugation procedures. The fractions were characterized by appropriate microscopic observation. Mitochondria were then isolated from these fractions by differential centrifugation of their homogenates. The two different types of mitochondria were characterized with respect to certain enzyme activities, respiratory rate, rate of protein synthesis, and their buoyant density in sucrose gradients. The mitochondria from the neuron-enriched fraction were distinguished by a higher rate of incorporation of amino acids into protein, higher cytochrome oxidase activity, and a higher buoyant density in sucrose density gradients. Mitochondria from the glia-enriched fraction showed relatively high monoamine oxidase and Na(+)- and K(+)-stimulated ATPase activities. The rates of oxidation of various substrates and the acceptor control ratios did not differ appreciably between the two types of mitochondria. The difference in the buoyant density of mitochondria isolated from the neuron-enriched and glia-enriched cell fractions was utilized in attempts to separate neuronal and glial mitochondria from the mixed mitochondria obtained from whole brain homogenates in shallow sucrose gradients. The appearance of two peaks of cytochrome oxidase, monoamine oxidase, and protein concentration in such gradients shows the potential feasibility of such an approach.

Spouses of first-ever stroke patients: psychological well-being in the first phase after stroke.

BACKGROUND AND PURPOSE: A stroke affects not only the patient but also the spouse. To better support the spouse during the acute phase of stroke, knowledge is needed about his or her experience with the situation. The aim of the present study was to study the well-being of the spouses of stroke patients during the acute state of stroke and to identify factors that may influence their well-being. METHODS: Eighty-three consecutively enrolled spouses of first-ever stroke patients <75 years old participated. Their psychological well-being, measured by the Psychological General Well-Being Index 10 days after the stroke, was compared with norm values. Multiple analyses of correlation were performed to investigate the effects on psychological well-being of (1) age and sex, (2) level of impairment of the stroke patient, and (3) intrapersonal variables such as previous life satisfaction and view of the future. RESULTS: The study group showed significantly lower psychological well-being compared with norm values except for the dimension of general health. The variables that correlated significantly with the Psychological General Well-Being total score were the sensorimotor impairment of the stroke patient and the "view of the future." This view of the future also correlated significantly with the level of functional ability of the stroke patients. CONCLUSIONS: During the acute phase of stroke, the severity of the stroke has an impact on the spouse's image of his or her future life, whereas the individual appraisal of personal consequences and of his or her own coping capacity seems to have a greater impact on the psychological well-being of the spouses than does the objective state of disability.

Resource utilization and costs of stroke unit care integrated in a care continuum: A 1-year controlled, prospective, randomized study in elderly patients: the Göteborg 70+ Stroke Study.

BACKGROUND AND PURPOSE: The aim of the present study was to examine resource utilization during a 12-month period after acute stroke in elderly patients randomized to care in an acute stroke unit integrated with a care continuum compared with conventional care in general medical wards. A secondary aim was to describe costs related to the severity of stroke. METHODS: Two hundred forty-nine consecutive patients aged >/=70 years with acute stroke within 7 days before admission, living in their own homes in Göteborg, Sweden, without recognized need of care were randomized to 2 groups: 166 patients were assigned to nonintensive stroke unit care with a care continuum, and 83 patients were assigned to conventional care. There was no difference in mortality or the proportion of patients living at home after 1 year. Main outcomes were costs from inpatient care, outpatient care, and informal care. RESULTS: Mean annual cost per patient was 170, 000 Swedish crowns (SEK) (equivalent to $25,373) and 191,000 SEK ($28,507) in the stroke unit and the general medical ward groups, respectively (P:=NS). Seventy percent of the total cost was for inpatient care, and 30% was for outpatient and informal care. For patients with mild, moderate, and severe stroke, the mean annual costs per patient were 107,000 SEK ($15,970), 263,000 SEK ($39, 254), and 220,000 SEK ($32,836), respectively (P:<0.001). There was no statistical difference in age or nonstroke diagnosis. CONCLUSIONS: The total costs the first year did not differ significantly between the treatment groups in this prospective study. The total annual cost per patient showed a very large variation, which was related to stroke severity at onset and not to age or nonstroke diagnoses. Costs other than those for hospital care constituted a substantial fraction of total costs and must be taken into account when organizing the management of stroke patients. The high variability in costs necessitates a larger study to assess long-term cost effectiveness.

Effect of acute stroke unit care integrated with care continuum versus conventional treatment: A randomized 1-year study of elderly patients: the Göteborg 70+ Stroke Study.

BACKGROUND AND PURPOSE: The aim of the study was to compare the effect of conventional treatment with the effect of acute stroke unit care integrated with geriatric stroke unit care continuum. METHODS: A 1-year study was undertaken with 2:1 randomization to stroke unit care or conventional care, with assessment by an independent team. The study was composed of 249 elderly patients (aged >/=70 years) hospitalized for acute stroke, without previous cerebral lesion and without recognized need of care. Main outcome measures were patients at home after 1 year, ability in daily living activities, health-related quality of life score according to questionnaire, death or institutional care, and death or dependence. RESULTS: One hundred two patients (61%) in the stroke unit and 49 patients (59%) in the general ward group were alive and at home after 1 year (95% CI -10% to 16%). There were no significant differences in daily life activities or quality of life. In patients with concomitant cardiac disease, there was a reduction in death or institutional care after 3 months in the stroke unit group compared with the group receiving conventional care (28% versus 49%, respectively; 95% CI -40% to -3%). This effect did not remain after 1 year. Patients seeking care after 24 hours often had mild stroke and lived alone. CONCLUSIONS: There was no effect on the number of patients living at home after 1 year, but after 3 months of stroke unit care, a beneficial effect was found on mortality and the need for institutional care among those with concomitant heart disease. This study involved patients who were considerably older than those investigated in previous randomized studies of acute stroke unit care; thus, these findings will contribute to the specialized register of controlled trials in stroke.

Cerebral atherosclerosis as predictor of stroke and mortality in representative elderly population.

BACKGROUND AND PURPOSE: The aim of this study was to assess the relationship between cardiovascular risk factors, atherosclerotic disease in the carotid bifurcation, and the risk of stroke and mortality in a representative population sample. METHODS: One hundred forty-two men and women participated in a population study at ages 70 and 76 years. At age 78, extracranial and intracranial circulation was examined by means of duplex sonography and transcranial Doppler techniques. Mortality and hospitalization for stroke were analyzed over a 5-year follow-up period up to age 83 years. RESULTS: Carotid plaques were identified in 82% of the men and 79% of the women. Bilateral plaques were found in 57% of the men and 46% of the women, and stenosis resulting in >50% diameter reduction occurred in 28% of the men and 17% of the women. Carotid stenosis >75% was observed in 7 subjects (0.5%). Bilateral plaques at age 78 were correlated with systolic blood pressure and ischemic heart disease at age 70 years. The pulsatility index was 1.0 to 1.4 in 63% and > or =1.5 in 13% of the study population. The pulsatility index was correlated with systolic and diastolic blood pressure, serum cholesterol, and triglycerides. Men with bilateral carotid plaques at age 78 years had an increased risk of stroke or mortality during the 5-year follow-up period (74% bilateral plaques versus 21% unilateral or no plaques). This was not found in the women (33% versus 26%). CONCLUSIONS: Carotid atherosclerosis was prevalent in a majority of elderly subjects. Bilateral plaques were correlated with systolic blood pressure and ischemic heart disease at age 70 years and predicted the risk of stroke and mortality in men but not in women.

Cerebrospinal fluid proteins and cells in men subjected to long-term exposure to organic solvents.

Cerebrospinal fluid (CSF) was obtained from 17 men occupationally exposed to organic solvents and diagnosed as having a psycho-organic syndrome. Healthy volunteers and patients without neurological disorders were used as controls. The albumin ratio was increased in three heavily exposed men, indicating an increased passage of albumin over the blood-brain barrier. A slight monocytoid reaction was present in three of the subjects in the exposed group. Myelin basic protein and enolase activity were within normal limits. Isoelectric focusing of CSF-enriched proteins obtained by absorption chromatography showed alterations in nine out of 17 exposed individuals: The most prominent change was a relative increase of the protein band with Ip 4.7.

Genetic variation at the human tissue-type plasminogen activator (tPA) locus: haplotypes and analysis of association to plasma levels of tPA.

Tissue-type plasminogen activator (tPA) plays a key role in thrombus dissolution and plasma levels of tPA have been associated with cardiovascular disease. We have previously resequenced regulatory and coding regions of the human tPA gene (PLAT) and identified eight single-nucleotide polymorphisms (SNPs). In a small experimental study, four common variants were associated with invasively determined vascular tPA release rates. The aim of the present study was to investigate whether there is an association between genetic variants at this locus and plasma levels of tPA. To this end, 240 Swedish individuals without cardiovascular disease were typed for the eight SNPs and an Alu insertion polymorphism at the PLAT locus, as well as for a polymorphism in the plasminogen activator inhibitor type 1 (PAI-1) promoter (PAI-1 -675 4G>5G). Stepwise regression analysis, with established predictors of plasma tPA including plasma PAI-1 and genetic variants, showed that neither genotypes nor haplotypes were major contributors to plasma tPA. The results also showed that the level of linkage disequilibrium was high at the PLAT locus, as demonstrated by the fact that only three haplotypes had a frequency above 5%. In conclusion, in the present study neither genetic variation at the PLAT locus nor the PAI-1 -675 4G>5G polymorphism was strong predictors of plasma tPA levels, which suggests that variations in other genes contribute to the heritability of this phenotype. The results also show that three haplotypes at the PLAT locus accounted for nearly 90% of the chromosomes and that they could be defined by typing only two SNPs.

Dementia of different etiologies: vasoactive intestinal polypeptide in CSF.

Patients with normal-pressure hydrocephalus, multi-infarct dementia, and recent cerebral infarction had significantly lower vasoactive intestinal polypeptide (VIP) levels than age-matched controls (11 +/- 3 pmol/l, 17 +/- 4 pmol/l, 21 +/- 4 pmol/l, and 33 +/- 4 pmol/l, respectively). Three months after a shunt operation, the VIP levels had increased significantly in patients with hydrocephalus (54 +/- 13 pmol/l). VIP concentration in patients with senile dementia did not differ from that of controls.

Increasing intrathecal lymphocytosis and immunoglobulin G production in neurologically asymptomatic HIV-1 infection.

Cerebrospinal fluid from 34 human immunodeficiency virus (HIV-1) seropositive patients, only four of whom had HIV-related neurological symptoms, was examined by cytology, protein quantification, isoelectric focusing and specific serological tests. CSF lymphocytosis and evidence of intrathecal IgG production, found in 21 and 20 respectively of the 34 patients, correlated significantly with the duration of the infection. Increasing IgG index was found in two patients with repeated CSF examinations during greater than 7 years. Intrathecal HIV antibodies were detected on Western blot in 32/34 patients. HIV antigen test positive in 5/34 sera was negative in all 34 CSF samples. Intrathecal B cell activation seems to increase during the early HIV infection.

Lateralization of cutaneous inflammatory responses in patients with unilateral paresis after poliomyelitis.

Unilateral paresis remaining after poliomyelitis may affect the expression of inflammatory diseases by lateralization of the disease manifestations. The purpose of this study was to assess the impact of the unilateral paresis after poliomyelitis on lateralization of neurogenic inflammation and immune responsiveness. The delayed-type hypersensitivity (DTH) reaction to tuberculin was used as an in vivo measure of antigen-specific T lymphocyte reactivity. Assessment of axon reflex vasodilatation was simultaneously employed to test for neurogenic inflammation. Fourteen of the 16 polio patients displayed a positive DTH reaction to tuberculin. All but two showed weaker DTH reaction on the paretic- compared to the contralateral-side (P = 0.001). Magnitude of electrically evoked axon reflexes significantly correlated to asymmetries of DTH responses. We conclude that damage of lower motor neuron leads to ipsilateral down-regulation of T cell-mediated cutaneous inflammation. This lateralization of DTH responses is related to deficiencies in motor and sympathetic innervation of the paretic extremity.

Hypotension induced by prostacyclin treatment during cardiopulmonary bypass does not increase the risk of cerebral complications.

High-dose prostacyclin treatment during cardiopulmonary bypass reduces platelet activation and possibly postoperative blood loss. A side-effect is arterial hypotension. We studied the incidence of cerebral complications in 79 patients requiring coronary bypass. Only patients without known cerebrovascular disease were studied. Thirty-nine patients received prostacyclin 50 ng/kg/min during cardiopulmonary bypass and 40 patients served as controls. Mean arterial blood pressure in the group given prostacyclin was below 30 mm Hg during the first 30 minutes of bypass but remained above 60 mm Hg in the control group. Postoperative neurological examination revealed transient cerebral dysfunction in six control patients and two prostacyclin-treated patients. Investigation of cerebrospinal fluid showed signs of blood-brain barrier damage in 12 control and seven prostacyclin-treated patients. Cytologic changes in cerebrospinal fluid consistent with brain tissue damage occurred in two control patients but in no patient given prostacyclin. Myelin basic protein and adenylate kinase in cerebrospinal fluid were assayed as being markers of brain damage. Myelin basic protein was within the normal range in all patients. Adenylate kinase was moderately increased (greater than 0.035 U/L) in five of 15 control patients and six of 13 prostacyclin-treated patients. We conclude that treatment with prostacyclin 50 ng/kg/min during cardiopulmonary bypass does not increase the risk of postoperative cerebral damage.

Amino acid incorporation into neurons and glia of guinea pigs with experimental allergic encephalomyelitis.

After in vitro incubation of brain slices from guinea pigs in the intermediate (10 days postinduction) stage of experimental allergic encephalomyelitis (EAE), incorporation of [14C]leucine into protein was increased in a glial-enriched fraction. By the late (17-18 days postinduction) stage of the disease, when EAE symptoms were manifest, both the neuronal- and glial-enriched fractions showed increased specific activity of their total protein. SDS polyacrylamide gel electrophoresis showed that the increased leucine incorporation occurred in those proteins which labeled in a control material. After intraperitoneal injection of [3H]leucine the incorporated radioactivity was slightly increased in unfractionated brains from EAE animals. The neuronal-glial ratios for protein-bound radioactivity indicated that the increased incorporation resided mainly in the glial population.

Cerebrospinal fluid proteins and cells in normal-pressure hydrocephalus.

A total of 21 patients with normal-pressure hydrocephalus were examined. Cerebrospinal fluid (CSF) was collected before and after operation with a ventriculoperitoneal shunt. A slight plasma-like protein pattern indicating a blood-brain barrier (BBB) dysfunction was seen in 38% of the patients before operation. No characteristic changes could be found in the "CSF-specific" protein fraction. After the shunt operation 65% of the patients had a BBB dysfunction to macromolecules and 70% had two additional acidic protein bands in the CSF-specific fraction. Ventricular CSF protein content was 73% of lumbar CSF content when shunts were patent. Isotope encephalography showed a radionuclide accumulation at the intracranial part of the shunt system, indicating that the BBB damage might be located round the shunt catheter.