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.

Does the cognitive measure Cog-4 show improvement among patients treated with thrombolysis after acute stroke?

BACKGROUND: Although the established measure of disability post stroke, the modified Rankin Scale emphasizes motor function and may underestimate the importance of cognitive impairment in more disabled patients. A subset of four items from the National Institutes of Health Stroke Scale has been proposed to assess cognitive function after stroke (Cog-4), and to correlate with modified Rankin Scale. Items correspond to orientation, executive function, language, and inattention. We investigated responsiveness of Cog-4 to treatment with thrombolysis and whether it offers information that supplements modified Rankin Scale. METHODS: We included 6268 patients from the Virtual International Stroke Trials Archive: 2734 received intravenous thrombolysis and 3534 were treated conservatively. We compared day 90 outcomes between treated and untreated groups, by modified Rankin Scale (illustrative) and by Cog-4 (primary measure) adjusting for age, baseline National Institutes of Health stroke scale, hemispheric lateralisation as well as baseline Cog-4 and baseline National Institutes of Health Stroke Scale excluding baseline Cog-4 separately. Analysis of Cog-4 was repeated within strata of 90 day modified Rankin Scale. Statistical analyses included proportional odds logistic regression and Cochran-Mantel-Haenszel test. RESULTS: Modified Rankin Scale showed a difference between treatment groups of expected magnitude (odds ratio 1·56; 95% confidence interval 1·43-1·72; P < 0·001). After adjustment for imbalance in baseline prognostic factors, the distribution of Cog-4 scores at 90 days was better in thrombolysed patients compared with nonthrombolysed patients (odds ratio 1·31; 95% confidence interval 1·18-1·47; P = 0·006). However, Cog-4 analysis stratified by 90-day modified Rankin Scale was neutral between treatment groups (OR 1·01; 95% CI 0·90-1·14), and Cog-4 was not responsive to treatment group even within modified Rankin Scale categories 4 and 5 despite substantial cognitive deficits in these patients. CONCLUSION: Although Cog-4 may be responsive to treatment effects, it does not provide additional information beyond modified Rankin Scale assessment.

Agreement in activities of daily living performance after stroke in a postal questionnaire and interview of community-living persons.

OBJECTIVE: To compare assessments of activities of daily living (ADL) made in a postal questionnaire and an interview. DESIGN: Comparative study of a convenience sample. SUBJECTS: Results in 36 persons with stroke >10 years previously. METHODS: Data on ADL were gathered in a self-administered postal questionnaire followed by a semi-structured interview (within 1-2 weeks) using items in the Functional Independence Measure, combined with instrumental items, Instrumental Activity Measure or the ADL taxonomy (personal and instrumental items). RESULTS: There was generally moderate to good agreement between the postal questionnaire and the interview. Other dependence identified was reported during the interviews. Although the operational descriptions of the items varied between the ADL indices, they primarily identified ADL independence in the same persons. CONCLUSION: The use of a self administrated postal ADL questionnaire was feasible for studying ADL performance. However, in some persons, interviews may be needed to complement the results.

Activity performance and upper extremity function in cervical spinal cord injury patients according to the Klein-Bell ADL Scale.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: (1) To examine whether the Klein-Bell ADL Scale (K-B Scale) discriminates cervical spinal cord injury (SCI) patients in daily activities and to explore its applicability in this group of patients. (2) To examine the association between basic ADL and upper extremity function. (3) To investigate if grip ability can be discerned in the scale. SETTING: Spinal Cord Injury Unit, Sahlgrenska University Hospital, Göteborg, Sweden. METHODS: Fifty-five patients with cervical SCI with no prior reconstructive hand surgery were included in the study. Analyses of the patient's independence were made according to the K-B Scale. Three additional analyses were carried out, the first examined whether the use of assistive devices and house and car adaptations influenced independence. The last two used different approaches to investigate whether arm and grip function could be detected in the K-B scale. RESULTS: Raw score in the K-B Scale can discriminate for independence in daily activities but the scale's weight scheme does not function for cervical SCI patients. Assistive devices and car and house adaptations can compensate for dependence in daily activities. Lack of grip function decreases the patient's ability to become independent. Diagnosis-related activities cannot be assessed in all items. CONCLUSION: The K-B Scale's raw score was useful assessing daily activities in cervical SCI patients. Its reliability in conjunction with arm and grip function in patients with cervical SCI has yet to be proven.

Clomethiazole Acute Stroke Study in ischemic stroke (CLASS-I): final results.

BACKGROUND AND PURPOSE: A previous trial (the Clomethiazole Acute Stroke Study) generated the hypothesis that clomethiazole is effective in patients with a major ischemic stroke (total anterior circulation syndrome), and this was tested in the present study. METHODS: A total of 1198 patients with major ischemic stroke and a combination of limb weakness, higher cortical dysfunction, and visual field deficits were randomly assigned to clomethiazole (68 mg/kg IV over 24 hours) or placebo. The study drug was initiated within 12 hours of symptom onset. Functional outcome and neurological recovery were assessed at days 7, 30, and 90, with the proportion of patients with a Barthel Index > or =60 at last follow-up as the primary outcome measure. RESULTS: The patients were randomly assigned equally, and the two treatment groups were well matched for baseline characteristics, including stroke severity (mean National Institutes of Health Stroke Scale score 16.9+/-5.2). Ninety-six percent were classified as total anterior circulation syndrome. The proportion of patients reaching a Barthel Index score of > or =60 was 42% in the clomethiazole-treated group and 46% in the placebo-treated group (odds ratio, 0.81; 95% CI, 0.62 to 1.05; P=0.11). There was no evidence of efficacy on any secondary outcome variables (modified Rankin Score, National Institutes of Health Stroke Scale, Scandinavian Stroke Scale, and 30-day CT infarct volumes) compared with placebo. Subgroup analysis showed a similar lack of treatment effect in patients treated early (<6 hours) and in those treated later (6 to 12 hours). Somnolence was an expected pharmacological effect of clomethiazole, and this occurred during treatment as an adverse event in half of the patients randomly assigned to study drug. CONCLUSIONS: The target population was selected, and sufficient drug was given to produce the expected pharmacological effect in the brain. Clomethiazole does not improve outcome in patients with major ischemic stroke.

Measures of order consistency between paired ordinal data: application to the Functional Independence Measure and Sunnaas index of ADL.

The aim was to evaluate the inter-item consistency between corresponding items in the Functional Independent Measure (FIM) and Sunnaas index of ADL (SI) by means of a statistical approach that takes account of the nonmetric properties of ordinal data. The ADL dependence in 204 stroke patients was assessed by interview 3 months after the onset of stroke. The result showed that the inter-item consistency between the FIM and SI were high for many items, but operational differences between some FIM and SI items were also identified. The statistical evaluation demonstrated that some of the ordered categorical levels of the seven-point item scales in the FIM could be aggregated into four levels without loss of information.

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.

The treatment of negative symptoms: a clinical and methodological study.

The primary objective of this study was to evaluate the efficacy, safety and tolerability of remoxipride (controlled release) versus haloperidol in patients with negative symptoms. The study comprised a multicentre, randomised, double-blind, parallel-group clinical trial. Two hundred and five patients were randomised to either remoxipride or haloperidol. Patients eligible for this study were aged 18-65 years, met the DSM-III-R diagnosis for chronic schizophrenia and the Positive and Negative Symptoms Scale (PANSS) criteria for predominant negative symptoms. There was a statistically significant reduction in the PANSS scores of at least 20% from baseline to last rating for 39 remoxipride (49.4%) and 45 haloperidol (47.6%) treated patients. There were no statistical differences found between the two treatment groups with respect to improvement of negative symptoms and adverse events. The PANSS data suggest that both remoxipride and haloperidol improve the cluster of negative symptoms concerned with social functioning. In addition, the design of the study provides a methodology that is appropriate to the study of primary negative symptoms in schizophrenia.

Clomethiazole acute stroke study (CLASS): results of a randomized, controlled trial of clomethiazole versus placebo in 1360 acute stroke patients.

BACKGROUND AND PURPOSE: The efficacy and safety of the neuroprotective drug clomethiazole was tested in a double blind placebo controlled trial in patients with a clinical diagnosis of acute hemispheric stroke. METHODS: Patients with symptom onset of /=60 points on the Barthel Index) at 90 days. RESULTS: A total of 1360 patients were included. In the main efficacy analysis (n=1353), 56.1% of patients taking clomethiazole and 54.8% of placebo patients reached relative functional independence. The difference was not statistically significant. An analysis of the effect of time since onset of symptoms showed no difference between the treatment groups. Clomethiazole was generally well tolerated and appeared safe in the population studied. Sedation was the most common adverse event, leading to treatment withdrawal that occurred in 15.6% of clomethiazole-treated patients compared with 4.2% of placebo-treated patients. In a subgroup classified before randomization as having total anterior circulation syndrome (TACS) (n=545, or 40% of all randomized patients), the percentage of those reaching relative functional independence was 40.8% on clomethiazole and 29.8% on placebo, a difference of approximately 11 percentage units. TACS patients have clinical symptoms suggesting a "large" stroke. CONCLUSIONS: Clomethiazole had no adverse or beneficial effect on long-term outcome for all patients but produced sedation. The hypothesis that clomethiazole is effective in patients with large strokes will be tested in a further study.

Influence of food intake on electrocardiograms of healthy male volunteers.

OBJECTIVE: To study the influence of food intake on electrocardiogram (ECG) variables (heart rate, QT-, QTc-, PR-intervals, QRS-time) and morphological alterations of the T-waves in 12 healthy male volunteers. METHODS: The study was of open, three-period crossover design. On each occasion, all subjects fasted from midnight. During two of the study periods, the subjects were given a standardised meal at 1.5 h and 5.5 h after the baseline assessments, respectively, whereas, during the third period, they remained fasting for the entire study period of about 9 h. ECG and blood pressure were recorded at baseline and thereafter every hour for 8 h. RESULTS: No ECG changes were observed following the fasting condition, whereas a clear change in ECG and an increased heart rate were recorded in response to the meal intake during the other two periods. The most prominent ECG effect was the change in the size and shape of the T-waves, which were described as flattened to biphasic and, occasionally, negative. These alterations were most pronounced in the precordial leads V4 to V6 in the ECG recording immediately following the meal intake, with a gradual return to baseline conditions over 4-5 h. Moreover, a transient increase of supine systolic blood pressure was also recorded in response to the meal intake. CONCLUSIONS: The intake of a meal can cause clear and consistent ECG changes in healthy male subjects, comprising increases in heart rate as well as alterations in the size and shape of the T-waves (flattened to biphasic and, occasionally, negative). Also, a post-meal increase in the supine systolic blood pressure was recorded.

The clomethiazole acute stroke study (CLASS): efficacy results in 545 patients classified as total anterior circulation syndrome (TACS).

The CLASS study showed no significant difference between treatment groups for the neuroprotectant clomethiazole compared with placebo. However, a beneficial effect of the drug was seen in patients with total anterior circulation syndrome (TACS). These are patients with clinical symptoms suggesting a large stroke. Full results of this subgroup analysis are reported. Patients were classified before randomization using clinical symptoms into the stroke syndromes TACS, partial anterior circulation syndrome, and lacunar syndrome. Subgroup analyses of stroke syndromes were performed post hoc after detecting a treatment by severity interaction. The primary efficacy variable was relative functional independence defined as the proportion of patients scoring > or =60 on the Barthel Index at 90 days. TACS patients (n=546, 40% of all CLASS patients) were more severe at baseline on the 58 point Scandinavian Stroke Scale compared with non-TACS patients (median difference 10 points, mean difference 10.9 points, SE=0.6). Outcome for TACS patients treated with placebo was poor, with only 29.8% reaching relative functional independence. This was increased to 40.8% in the clomethiazole group, a 37% relative benefit, which is clinically significant (odds ratio=1.62, 95% CI 1.13-2.31, nominal P=.008). There was little or no difference in the outcome of non-TACS patients treated with clomethiazole compared with placebo. The treatment effect in TACS patients was quite consistent across participating countries and the 3 parts of the study defined by the 2 interim analyses. The treatment effect seen in patients with clinical symptoms suggesting a large stroke (TACS) is biologically plausible but requires confirmation in a prospective study which is ongoing.

Effects of acupuncture treatment on daily life activities and quality of life: a controlled, prospective, and randomized study of acute stroke patients.

BACKGROUND AND PURPOSE: A number of studies have indicated that acupuncture might improve the functional recovery of stroke patients. These studies vary in inclusion criteria, sample size, and evaluation methods. The present study was designed to investigate whether electroacupuncture treatment favorably affects stroke patients' ability to perform daily life activities, their health-related quality of life, and their use of health care and social services. METHODS: One hundred four consecutive patients >40 years of age admitted to hospital because of an acute stroke were randomized to 3 groups: deep, superficial, and no acupuncture treatment. The acupuncture treatment given by 4 physiotherapists started 4 to 10 days after randomization and was given twice a week for 10 weeks. All patients underwent conventional stroke rehabilitation as well. Two occupational therapists, blinded regarding the patients' allocation, evaluated the treatment effects. The assessments were performed 4 times during the first year after randomization by means of interviews and observations. RESULTS: There were no differences between the groups with reference to changes in the neurological score and the Barthel and Sunnaas activities of daily living index scores after 3 and 12 months. Regarding the Nottingham Health Profile, the no acupuncture group had somewhat fewer mobility problems. No differences in health care and social services were found between the groups. CONCLUSIONS: The present study does not give support to the previous studies, which indicates that acupuncture treatment may have a beneficial effect on acute stroke patients' ability to perform daily life activities, their health-related quality of life, and their use of health care and social services.

The clomethiazole acute stroke study in ischemic, hemorrhagic, and t-PA treated stroke: Design of a phase III trial in the united states and canada.

Clomethiazole is a drug with sedative properties effective in laboratory studies of brain ischemia. A large European multicenter trial of clomethiazole in acute stroke patients showed no benefit overall, but subgroup analysis indicated that patients with large infarctions may have benefited from treatment. To confirm this preliminary finding, we have designed CLASS-IHT, the Clomethiazole for Acute Stroke Study in Ischemic, Hemorrhagic and TPA Treated Patients, to be conducted in North America. Patients who suffer large cerebral infarctions and present within 12 hours of symptom onset are eligible. Patients will be randomized to receive clomethiazole 68 mg/kg over 24 hours or vehicle, using a dosing scheme based on the pharmacokinetics measured in the first trial. Outcome assessments include stroke scales, the Barthel Index, and lesion volume. An additional study of health economic outcomes is planned. The primary endpoint for CLASS-I will be the Barthel Index 90 days after stroke. A total of 1,200 patients will be randomized to CLASS-I, and in safety-only trials, 200 patients with cerebral hemorrhage will be randomized into CLASS-H and another 100 to 200 patients will be randomized into CLASS-T. The details of the protocols for all three studies are presented.

Triple hybridization with cultivated barley (Hordeum vulgare L.).

A crossing programme for trispecific hybridization including cultivated barley (Hordeum vulgare L.) as the third parent was carried out. The primary hybrids comprised 11 interspecific combinations, each of which had either H. jubatum or H. lechleri as one of the parents. The second parent represented species closely or distantly related to H. jubatum and H. lechleri. In trispecific crosses with diploid barley, the seed set was 5.7%. Crosses with tetraploid barley were highly unsuccessful (0.2% seed set). Three lines of diploid barley were used in the crosses, i.e. 'Gull', 'Golden Promise' and 'Vada'. Generally, cv 'Gull' had high crossability in crosses with related species in the primary hybrid. It is suggested that 'Gull' has a genetic factor for crossability not present in cv 'Vada' and cv 'Golden Promise'. One accession of H. brachyantherum used in the primary hybrid had a very high crossability (seed set 54.7%) in combination with cv 'Vada' but no viable offspring was produced. In all, two trispecific hybrids were raised, viz. (H. lechleri x H. brevisubulatum) x 'Gull' (2n=7-30) and (H. jubatum x H. lechleri) x 'Gull' (2n=20-22). The first combination invariably had a full complement of seven barley chromosomes plus an additional chromosome no. 7, but a varying number of chromosomes (19-22) of the wild-species hybrid. The second combination had a full set of barley chromosomes. The meiotic pairing was low in both combinations.

cDNA clone for the human invariant gamma chain of class II histocompatibility antigens and its implications for the protein structure.

The invariant gamma chain is transitorily associated with class II histocompatibility antigens during intracellular transport. We have isolated and sequenced a cDNA clone corresponding to the human gamma chain. mRNA hybridizing to the cDNA clone translated into a 33,000-dalton chain that associated specifically with class II antigen alpha and beta chains. The gamma chain consists of 216 amino acids. The two N-linked carbohydrates are attached to asparagines 114 and 120. A continuous stretch of hydrophobic and neutral amino acids occurs in positions 31-56 from the NH2 terminus. This region seems to constitute the transmembrane portion of the polypeptide chain. The positions of the carbohydrate moieties and the putative transmembrane segment indicate that the NH2 terminus of the gamma chain resides on the cytoplasmic side of the membrane. Cell-free translations in conjunction with radiochemical amino acid sequence analyses suggest that the gamma chain lacks an NH2-terminal signal sequence.

Association of human gamma chain with class II transplantation antigens during intracellular transport.

Cell surface expressed human and murine class II transplantation antigens are composed of two polypeptide chains called alpha and beta. During intracellular transport an invariant chain, provisionally called gamma, is associated with the class II antigen chains. Since gamma chains leave the endoplasmic reticulum only when associated with alpha and beta chains, we have studied the intracellular transport of the gamma chain and its possible cell surface expression. Modifications of the carbohydrate moieties of the gamma chain during intracellular transport were also examined. The gamma chain appears to contain two Asn-linked carbohydrate moieties and maybe also one or more Ser/Thr-linked carbohydrates. At all times during the pulse-chase experiments core glycosylated gamma chains resolved into two distinct spots on two-dimensional gel electrophoresis. The occurrence of core-glycosylated gamma chains was expected since more gamma chains than alpha and beta chains exist in the endoplasmic reticulum. Terminally glycosylated, alpha, beta, and gamma chains emerged simultaneously supporting the idea that the three types of chains are brought to the Golgi complex bound to each other. However, terminal glycosylation is temporally related to the dissociation of the gamma chain from the alpha and beta chains. Since isolated plasma membranes contained molecules indistinguishable from gamma chains, it is concluded that gamma chains are transported together with class II antigens from the endoplasmic reticulum to the Golgi complex. After dissociation, class II antigens and some, if not all, gamma chains seem to become independently integrated into the plasma membrane.

Effects of the glucosidase inhibitors nojirimycin and deoxynojirimycin on the biosynthesis of membrane and secretory glycoproteins.

The glucosidase inhibitors nojirimycin (NM) and 1-deoxynojirimycin (dNM) interfere with N-linked glycosylation. The effects of NM and dNM on the biosynthesis of secretory glycoproteins (IgD and IgM) and membrane glycoproteins (HLA-A, B, C and -DR antigens) have been examined. Whereas treatment of IgD- and IgM-producing cells with NM results in the transfer of drastically shortened oligosaccharide side chains, treatment with dNM inhibits trimming, most probably through interaction with glucosidase I and/or II. A comparison of NM and dNM with tunicamycin and the mannosidase inhibitor swainsonine (SW) show that each of the inhibitors interferes with N-linked glycosylation in a distinct manner. For both Ig and HLA antigens, the effects of SW are discernible at the final stages of glycan maturation only, whereas the effects of dNM are observed quite early in the biosynthetic process. The secretion of IgD, but not IgM, was blocked in dNM-treated cells. The HLA-A, B, C heavy chains synthesized by the Daudi cell line were degraded in an accelerated fashion in dNM-treated cells, but no effects were seen on the HLA-DR antigens in these cells. Although both SW and dNM interfere with trimming, further modifications of the oligosaccharide side chains occur, and show that the two processes are not obligately coupled. Glucosidase inhibitors such as NM and dNM, as well as the mannosidase inhibitor SW, allow modification of glycan structure, and may be used to study the biological role of glycoprotein oligosaccharides and their modifications.