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Background and Purpose: The neuronal death that accompanies an ischemic stroke has previously been attributed to a necrotic process. However, numerous studies in experimental models of ischemia have recently indicated that programmed cell death, also called apoptosis, may contribute to neuronal death. The aim of the present study was to investigate the intrathecal levels of proteins regulating apoptosis in acute stroke and to relate these levels to brain damage and to production of proinflammatory and anti-inflammatory cytokines., Methods: Thirty stroke patients were studied prospectively on days 0 to 4, 7 to 9, 21 to 26, and after day 90 with clinical evaluation, radiological assessment, and analysis of cerebrospinal fluid (CSF) levels of soluble (s) Fas/APO-1 and sbcl-2, 2 proteins that regulate apoptosis. In addition, analysis of the intrathecal levels of cytokines interleukin (IL)-1beta, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha was performed. Nineteen CSF samples from healthy subjects were used for control purposes. The patients were examined with MRI 1 to 3 months after stroke onset for measurement of infarct volume, Results: Significantly decreased CSF levels of sFas/APO-1 were observed during the entire observation period, with a maximal decrease on day 21 after the onset of stroke. The intrathecal levels of sFas/APO-1 were significantly negatively correlated with the volume of brain infarct and with the neurological deficit 3 weeks and 3 months after the onset of the stroke. In addition, the intrathecal levels of sFas/APO-1 were significantly correlated with the levels of IL-1beta, IL-6, IL-10, and GM-CSF 3 weeks after the onset of the disease. The intrathecal levels of sbcl-2 were significantly decreased during the first 3 days after stroke onset and at the same time were positively correlated with the levels of IL-6 and tumor necrosis factor-alpha., Conclusions: Our study demonstrates decreased intrathecal levels of proteins with antiapoptotic properties, suggesting that patients with acute stroke display a propensity toward apoptosis. Control of factors regulating apoptosis may lead to decreased delayed brain damage in stroke.

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.

Simple reaction time was examined in a consecutive series of 60 right hemisphere stroke patients at the postacute stage and at 6 to 7 months poststroke. Reaction times to auditory stimuli were measured within the ipsilesional side of space. Patients showing contralateral neglect in conventional tests of neglect showed significantly increased reaction times at the postacute stage and at the follow-up compared to those not showing neglect and to those in a group of normal controls. The results suggest that a lowered general attentional capacity may constitute a central component behind persistent neglect. An additional analysis of the CT scans of the patients showed that a large lesion including the paraventricular white matter in the temporal lobe was the most important anatomical correlate of persisting slow reactions.

We have previously demonstrated that brain lesions caused by stroke led to the lateralization of T-cell dependent inflammation. The purpose of this study was to assess the impact of localization of the brain lesion on lateralization of immune responsiveness. The delayed-type hypersensitivity (DTH) reaction was used as an in vivo measure of antigen specific T-lymphocyte reactivity. All stroke patients were examined with computed scan tomography (CT) of the brain to ascertain the localization and extent of the brain lesion. Patients with right-sided brain lesions displayed significantly larger (P = 0.008) DTH responses on the paretic side compared to the contralateral side. Detailed analysis of the localization of the brain lesion revealed that infarcts encompassing frontal lobe-putamen led to significantly larger (P = 0.007) DTH responses on the paretic side compared to the contralateral side. Localization of the brain lesion affects the lateralization of DTH, supporting an asymmetrical modulation of the immune response. In addition, our study points to the frontal cortex-putamen as a putative brain centre regulating the magnitude of immune responses.

A growing body of evidence points out the potential role of inflammatory mechanisms in the pathophysiology of ischaemic brain damage. We have recently demonstrated that stroke patients display an intrathecal production of proinflammatory cytokines, such as IL-1beta and IL-6 already within the first 24 h after the beginning of symptoms (Tarkowski et al., 1995). The aim of the present study was to investigate patterns of local inflammatory responses as a consequence of acute stroke. Thirty stroke patients were studied prospectively on days 0-3, 7-9, 21-26 and after day 90 with clinical evaluations, radiological assessments and analysis of cerebrospinal fluid (CSF) cytokine levels. In addition, 15 healthy control CSF samples were used. Significantly increased CSF levels of IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-10 were observed early during the stroke with a peak on day 2 for the proinflammatory cytokines IL-8 and GM-CSF, and on day 3 for the immunoregulatory cytokine IL-10. Patients with a brain infarct predominantly located in the white matter showed significantly higher levels of IL-8 in CSF than patients with an infarct mainly located in the grey matter. Also, high levels of intrathecal tumour necrosis factor-alpha (TNF-alpha) were associated with the presence of white matter disease. Our study demonstrates an intrathecal production of proinflammatory and immunoregulatory cytokines in patients with stroke, supporting the notion of localized immune response to the acute brain lesion. A better understanding of the inflammatory response in stroke may lead to new treatment strategies.

Anatomical and neurological correlates of visuospatial neglect were studied in 53 patients with a CT-documented right hemisphere stroke. Evidence of neglect at the acute stage poststroke was strongly related to large lesions involving the middle temporal gyrus and/or the temporo-parietal paraventricular white matter. Thus, out of 18 patients with evidence of visuospatial neglect at the acute stage, 12 showed a lesion in the middle temporal gyrus and/or the deep temporo-parietal white matter. Among the 35 patients that failed to show visuospatial neglect, only one patient had a lesion within these areas. Comparing those patients who recovered from neglect with those that did not, a high correlation was found between persisting neglect and a lesion involving the paraventricular white matter in the temporal lobe. On the basis of above findings, it was suggested that a simultaneous damage to the cortico-thalamic system for regulation of arousal and to the neural systems mediating visual orienting, is likely to be followed by persisting neglect symptoms.

Cerebral lesions causing aphasia are often found close to auditory areas. The aphasia may therefore sometimes be aggravated by hearing problems, which are concealed by communicative restrictions. Unilateral lesions of the cerebral auditory system influence the functional ear preference disclosed by dichotic tests. For that reason we have examined aphasic patients with recent, initial, unilateral brain infarctions for ear preference with regard to dichotically presented two syllable words. In a consecutive series of 114 patients who could cope with the test, 29 showed signs of an acquired left ear advantage (LEA). All were offered, and 22 accepted a full scale audiological examination including pure tone, speech and phase-audiometry. Nine of these patients showed retrocochlear or central hearing disturbances, which added to their communicative predicaments. The LEA of 11 patients lacked audiological rationales and a compensatory shift of cerebral speech-lateralization cannot be excluded.

Background and Purpose: Recently, asymmetries have been demonstrated in skin sudomotor and vasomotor function after unilateral cerebral lesions. The present study was performed to determine whether other bedside tests reflecting sympathetic and parasympathetic cardiovascular functions would reveal differences with respect to the side of cerebrovascular lesions., Methods: Heart rate variability during deep breathing as well as blood pressure and heart rate changes during tilt and isometric handgrip was measured in a group of patients with a monofocal stroke and compared with similar data from age-matched patients with transient ischemic attack and healthy control subjects., Results: Compared with left-sided stroke and with the control subjects, stroke location on the right side was associated with a reduced respiratory heart rate variability (P > .01), a reflex mainly under parasympathetic control. In contrast, reflexes mainly reflecting peripheral sympathetic function were equal for right- and left-sided lesions., Conclusions: Since an imbalance in cardiac autonomic innervation may be crucial for the generation of cardiac arrhythmias and since reduced heart rate variability has been associated with increased mortality, the findings suggest that the risk of sudden death may be correlated with lateralization and location of the brain infarct after stroke.

Background and Purpose: Symptoms interpreted as unilateral disturbances of autonomic function, such as coldness, dryness, sweating, and trophic changes, are well known but incompletely understood clinical problems after stroke. The present study provides data related to the incidence and mechanisms behind such symptoms., Methods: Temperature perception thresholds, skin temperatures, evaporation rates, and skin blood flow responses were measured bilaterally in 37 stroke patients aged 58 +/- 13 years (mean +/- SD) and in a control group of 15 patients aged 64 +/- 15 years with a single transient ischemic attack., Results: Of the 37 stroke patients, 43% reported a sensation of coldness in the contralesional side of the body. Basal skin blood flow and temperature were relatively lower in the contralesional side. There was an excess of evaporation in the contralesional side after brain stem lesions and in the ipsilesional side after hemispheric lesions. Vasomotor reflex asymmetries occurred in 34% of the patients and were due to weak vasodilator or vasoconstrictor reflexes in the ipsilesional side. These abnormalities correlated significantly to sensations of unilateral coldness, hypalgesia, and thermohypesthesia in the contralesional side and anatomically to lesions in spinothalamo-cortical pathways., Conclusions: Focal central nervous system lesions due to stroke may result in symptoms and measurable evidence of unilateral disturbance of skin sympathetic function. Vasomotor asymmetries are probably due to lesions of vasomotor pathways descending uncrossed. Subjective coldness may be due to disturbed central processing.

Background and Purpose: We have previously demonstrated that stroke influences systemic immune responses. The aim of the present study was to investigate patterns of local inflammatory response as a consequence of acute stroke., Methods: Thirty stroke patients were studied prospectively on days 0 to 3, 7 to 9, 21 to 26, and after day 90 with clinical evaluations, radiological assessments, and analysis of serum and cerebrospinal fluid cytokine levels., Results: Significantly increased levels of interleukin-6 (IL-6) in cerebrospinal fluid (P < .001) were observed in virtually all patients studied compared with healthy control subjects. This increase was observed during the whole observation period but was significantly more pronounced within the first days after stroke onset, with a peak level on days 2 and 3. This initial increase was significantly correlated (r = .65, P = .002) with the volume of infarct measured by MRI 2 to 3 months later. Serum levels of IL-6 in stroke patients were significantly lower than cerebrospinal fluid levels of IL-6 (P = .013) and did not display any significant correlation to the size of the brain lesion. Also, increase in intrathecal but not systemic production of IL-1 beta was observed early during the stroke. Only minor increases of cerebrospinal fluid interferon-gamma levels were observed in two patients., Conclusions: Our study demonstrates an intrathecal production of IL-6 and IL-1 beta in patients with stroke, supporting the notion of localized inflammatory response to acute brain lesion. In addition, the significant correlation between early intrathecal production of IL-6 and the subsequent size of the brain lesion can be used as a prognostic tool, predicting the size of the brain damage before it is possible to accurately visualize it with radiological methods.

The impact of the acute and chronic phase of stroke on in vivo mediated immune functions was prospectively analysed in patients with mono- and multifocal brain lesions. The cutaneous delayed-type hypersensitivity (DTH) reaction to purified protein derivate was used as an in vivo measure of antigen specific T cell reactivity. Stroke patients have been tested prospectively for DTH reactivity at two separate occasions, 6-12 months apart. Both sides of the body were tested at each occasion. The DTH response on the paretic side changed significantly with time, from being smaller on the paretic side as compared with the contralateral one early after the onset of stroke, to become significantly larger (p = 0.017) in the chronic phase of the disease. In addition, stroke patients showed a significantly larger (p = 0.001) DTH reactivity bilaterally in the chronic phase of the stroke than in the early phase. When patients with single brain lesion and multiple brain lesions were analyzed separately, the increase of DTH reactivity on the paretic side between the 2 challenges was significant (p = 0.016) only in patients with the monofocal disease. We conclude that stroke induces i. an inhibition of DTH reactivity on the paretic side as compared with the non-paretic one in the acute phase but a lateralized enhancement of the DTH reactivity in the chronic phase of the disease, ii. a systemic increase of DTH reactivity in the chronic phase of the disease. Clinical factors positively correlated with these aberrations are: i. right sided, subcortical brain lesion, ii. paresis associated with impaired sensitivity, iii. minor stroke.

Background and Purpose: A number of clinical observations indicate that stroke affects the course of immune-mediated diseases by lateralization of the disease manifestations, such as arthritis. The purpose of this study was to assess the impact of early stroke on lateralization of immune responsiveness., Methods: The delayed-type hypersensitivity (DTH) reaction to purified protein derivative was used as an in vivo measure of antigen-specific T-lymphocyte reactivity. Assessment of axon reflex vasodilation was simultaneously used to test for cutaneous sympathetic activity., Results: There were no significant differences with regard to lateralization of DTH reactivity when all stroke patients were tested. However, patients with minor stroke displayed a significant (P < .001) decrease of DTH reaction on the paretic side compared with the contralateral side. In contrast, patients with major stroke showed a significant increase (P = .022) of DTH reaction on the paretic side. Patients with left hemiparesis had a significantly greater (P = .045) DTH response on the affected side than patients with a right hemiparesis. In addition, only the patients with motor deficit but not with sensory deficit or aphasia displayed side differences in DTH responses. When electrically evoked axon reflexes were studied in relation to DTH reactions, a significant correlation (r = .64; P < .001) was found between side asymmetries of DTH responses and side asymmetries of axon reflexes in an innervated skin area. No similar relation was present in skin areas where cutaneous sympathetic activity had been blocked by regional anesthesia., Conclusions: Early stroke lateralizes T-cell-mediated cutaneous inflammation. This effect depends on (1) the localization of the brain lesion, (2) the clinical course of the disease, and (3) the presence of motor deficit and may be mediated by (4) alteration of the cutaneous sympathetic nerve traffic.