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Background and purpose. Sensorimotor stroke (SMS) is often included among the lacunar syndromes, although the underlying cause of this stroke-subtype is less well documented. To this end we analysed 32 patients presenting with a sensorimotor syndrome. Methods. The study protocol included vascular risk factors, echocardiography, Doppler sonography of carotid arteries, CT scan and MRI of the brain. Results. There were 23 men and 9 women, mean age 65.7 years. Hypertension was present in 28% and diabetes in 19%. In all, 63% had sensorimotor deficit of faciobrachiocrural areas and 37% had faciobrachial or brachiocrural deficits. MRI disclosed a presumably relevant infarct in 26 patients (81%); 20 patients (62%) localized to the territory of small perforating arteries, 3 patients (9.5%) in the internal borderzone, and 3 patients (9.5%) in cortical territories. Eight of 20 deep infarcts were larger than 15 mm. No hemorrhage or non-vascular lesion was found. A potential cardioembolic source was present in 5 patients (16%), whereas 2 patients (6%) had an ipsilateral carotid stenosis > 50%. Conclusions. Small vessel disease was the most likely cause in 69% of our patients with SMS, whereas 31% had a potential cardioembolic source, large artery disease or infarcts not compatible with perforating artery disease.

Background: There are few long-term follow-up studies of patients with lacunar infarcts (LIs). The purpose of this 5-year follow-up study was to assess functional and cognitive outcome in relation to MRI findings. Methods: 81 patients with a first-ever LI were followed for 5 years with respect to mortality, stroke recurrence, functional and cognitive outcome. T2-weighted MRI was performed at baseline and at 5 years. The presence of basal ganglia lesions and white matter lesions was scored according to the European Task Force rating scale. Functional outcome was assessed with the Oxford Handicap Scale (OHP). Cognition was assessed with the Mini Mental State Examination (MMSE). Results: The 5-year mortality was 19%. Predictors for death were age (OR = 1.07, 95% CI 1.03–1.11), ischemic heart disease (OR = 2.1, 95% CI 1.1–4.1) and impairment score (OR = 1.16, 95% CI 1.02–1.32). 30% of the patients had a recurrent stroke. Predictors for recurrent stroke were diabetes mellitus (OR = 1.7, 95% CI 1.2–7.4) and amount of white matter lesions (OR = 1.7, 95% CI 1.2–2.7). 36% of the patients were functionally dependent (defined as OHP >2). Predictors for functional dependency were impairment score (OR = 1.71, 95% CI 1.12–2.59), MMSE (OR = 0.55, 95% CI 0.33–0.91) and stroke recurrence (OR = 84, 95% CI 9.4–745). 16% of the patients had cognitive impairment (defined as MMSE Conclusions: Many LI patients have a good functional outcome at 5 years. For older patients, for patients with an initial severe stroke, and with additional vascular risk factors, however, the prognosis is more severe, with an increased risk for mortality, stroke recurrence, and physical and cognitive decline.

The diseases studied in this thesis, Guillain-Barre Syndrome (GBS), Multiple Sclerosis (MS) and Polyneuropathy associated with monoclonal gammopathy of uncertain significance (PNMGUS), are of autoimmune origin with myelin components as putative auto antigens. T cells are important for the pathogenesis, as well as the cytokine network and autoantibodies. For all of these diseases, the immunopathogenisis is not fully understood and even if there are treatments available, none of them are curative and there are side effects. Thus there is a need for further clues in the immune mechanisms. Contrary to PNMGUS and MS, GBS is generally self-limiting. The mechanisms of the beneficial effect of interferon-beta (IFN-s) treatment in MS are not fully understood, (although alterations in the cytokine levels are subject to many reports). In PNMGUS, the proliferation of a monoclonal B cell clone and its antibody production are of great significance, however additional immune mechanisms are also of interest like the role of T cells and the role of B cells as antigen presenting cells.In studies of cytokines, frozen cells are often used, sometimes for practical reasons, so also in this thesis. Therefore effects of cryopreservation on cellular expression/secretion of cytokines were studied. The expression before compared to after cryopreservation of IFN-γ, IL-4, IL-5, IL-9, IL-10 and IL-13 was analysed with ELISA, ELISPOT and/or real time RT-PCR We found that the process of cryopreservation and thawing does affect the expression of cytokines, both at the protein and the mRNA level. The most consistent fmding was that expression of IL-4 was generally decreased in spontaneous and auto-antigen/allergen induced expression in cryopreserved cells. Thus, this study points out the importance of investigation of the effects of freezing for each cytokine, stimuli and patient group before using frozen cells in studies of in vitro cytokine secretion.The secretion of IL-4, IFN-γ, TGF-s, IL-6, and TNF-α during the course of GBS was analysed with ELISPOT and cell-ELISA. Our findings indicate a down-regulatory role for TGF-s and IL-4 in GBS.The longitudinal effects over one year of IFN-s treatment on secretion of IL-4, IFN-γ and IL-10 was analysed with the ELISPOT technique and IL-13 and IL-17 was analysed in cell supernatants with ELISA. A general finding was that surprisingly few changes occurred, and that most changes occurred early (6 weeks - 3 months). However, we found a shift in the cytokine balance towards more IL-4 and IL-10 secretion and/or less IFN-γ secretion during the treatment as the ratios of IL-4/IFN-γ as well as of IL-10/IFN-γ were increased. The interesting pro-inflammatory cytokine IL-17, associated with T cell mediated autoimmunity, has not been previously investigated during IFN-s treatment in MS and our findings of decreased IL-17 levels after one year of treatment could be a beneficial result of the IFN-s treatment.B cell clones from a patient with PNMGUS were successfully established by isolating B cells with myelin protein zero (P0) coated magnetic beads and subsequently transforming with Epstein-Barr virus (EBV). The clones were characterised and for instance they strongly expressed HLA-DR and CD80, compatible with antigen-presenting properties. The cell lines may provide useful tools in studies of PNMGUS.

Patients treated with oral anticoagulants (ACs) have an increased risk of intracerebral hemorrhage (ICH), which is more often fatal than spontaneous ICH. Options to reverse the AC effect include intravenous administration of vitamin K, plasma, and coagulation factor concentrate. However, the optimal management of AC-related ICH has not been determined in any randomized trial. In this study, the present management of AC-related ICH was surveyed, and determinants of survival were assessed.We retrospectively reviewed the medical records of all AC-related ICHs at 10 Swedish hospitals during a 4-year period, 1993 to 1996. Survival status after the ICH was determined from the Swedish National population register.We identified 151 patients with AC-related ICH. Death rates were 53.6% at 30 days, 63.6% at 6 months, and 77.5% at follow-up (mean 3.5 years). The case fatality ratio at 30 days was 96% among patients unconscious on admission (n=27), 80% among patients who became unconscious before active treatment was started (n=15), 55% among patients in whom no special action was taken except withdrawal of AC treatment (n=42), and 28% among patients given active anti-coumarin treatment while they were still conscious (n=64). The case fatality ratio at 30 days was 11% in the group treated with plasma (n=18), 30% in the group treated with vitamin K (n=23), and 39% in the group treated with coagulation factor concentrate (n=23). Within the first 24 to 48 hours after admission, 47% of the patients deteriorated. Choice of therapy to reverse the AC effect differed substantially between the hospitals (P0.0001), as did the time interval from symptom onset to start of treatment. Multiple logistic regression analysis showed only 2 factors (intraventricular extension of bleeding and ICH volume) that were independently related to case fatality at both 30 days and 6 months. The results were similar when the analysis was restricted to patients who were conscious on admission.In AC-related ICH, a progressive neurological deterioration during the first 24 to 48 hours after admission is frequent, and the mortality is high. Choice of therapy to reverse the AC effect differed considerably between the hospitals. There was no evidence that any treatment strategy was superior to the others. A randomized controlled trial is needed to determine the best choice of treatment.

There is a persistent need to find usable ways of measuring social network and support for children. Up to now virtually nothing is known about the social network from the child's viewpoint. In order to evaluate whether drawing a structured social network map (the Five Field Map) could serve as a way of elucidating important aspects of the social world of children, the maps of different samples of children were studied. In a school class of 27 children, aged 11 years, a test-retest study was undertaken. The essential aspects of the map showed good stability over time. The map was compared with other instruments of social interaction in different samples. Predicted associations were found in the nonclinical samples. Aspects of the map measuring dissatisfaction, negative contacts, and conflicts were found to be associated with behaviour problems. The closeness factor of the map and reported dissatisfaction and conflicts differentiated a normal group of children living in single-parent families from a similar group of children with psychiatric problems. The Five Field Map contributes important knowledge about how children perceive their social world. It can thus be considered a suitable instrument to describe the social network from the child's point of view.

We report presumed mechanisms of recurrent stroke in a prospective study on patients with lacunar infarction. Eighty-one patients with clinical and magnetic resonance imaging (MRI) findings compatible with lacunar infarction were followed for a median time of 48 months. Patients with recurrent stroke were assessed clinically by computed tomography, contrast-enhanced MRI and with respect to large-artery disease and cardioembolic sources of embolism. During follow-up, 9 patients (11.1%) died and 20 patients (24.7%) had 27 recurrent strokes (3 hemorrhagic, 24 ischemic). The annual risk of recurrent stroke was 6.8% and approximately even with time. Univariate analysis revealed age as the only risk factor significantly associated with recurrent stroke. Out of 24 episodes of recurrent ischemic stroke, 16 had clinical and neuroimaging features compatible with small penetrating artery occlusion, 6 were due to cortical infarcts, 1 episode was caused by presumed cerebral amyloid angiopathy, and 1 by a retinal infarct. Relevant large-artery disease was diagnosed in 2 patients with recurrent, small brainstem infarcts and in 2 patients with recurrent cortical and retinal infarcts. Although presumed lacunar infarcts predominated, our series highlights the heterogeneity of recurrent strokes after lacunar infarcts.

Quantitative data on sensory impairment in stroke patients are limited. We measured the perception thresholds for temperature and thermal pain in patients with different lacunar syndromes, correlated the results with clinical and magnetic resonance imaging (MRI) findings, and studied the long-term prognosis of sensory dysfunction. Quantitative thermal testing was performed by means of the Marstock method in 39 patients with lacunar syndromes (pure motor, sensorimotor, or pure sensory stroke) and MRI findings compatible with occlusion of a single perforating artery. Thresholds for cold, warmth, and heat pain were obtained bilaterally from the cheek, hand, and leg. The unaffected side was used as control. Follow-up included clinical assessments and repeated quantitative thermal testing (in 17 patients) up to 1 year after stroke onset. Patients with pure sensory stroke and sensorimotor stroke (n = 22) had a significant thermal hypoesthesia on the affected side for all modalities and test locations. Patients with pure motor stroke (n = 17) exhibited thermal hypoesthesia for cold and heat pain in the hand and for cold perception in the leg. On MRI, infarcts causing pure motor and sensorimotor stroke were predominantly lenticulocapsular, while a thalamic site of infarction was found in pure sensory stroke. The prognosis of sensory impairment was favorable, except for poststroke pain syndromes in three patients. Quantitative thermal testing confirmed an involvement of spinothalamic pathways in lacunar infarcts causing pure sensory and sensorimotor stroke and revealed a subclinical sensory impairment in patients with pure motor stroke. Infarction sites were similar in patients with pure motor and sensorimotor stroke.

There are only a few reports on long-term prognosis and functional outcome after lacunar infarction, and little is known about the evolution of MRI abnormalities with time in this subtype of stroke. To address these issues, we performed a 1-year clinical and MRI follow-up study in 81 patients with presumed lacunar infarction. AT 1 year after stroke onset 1 patient had died, whereas 5 patients (6.2%) had had recurrent strokes. Based on the Oxford Handicap Scale, 63 (79%) of the surviving patients were functionally independent at the time of follow-up. MRI at 1 year revealed new, clinically silent infarcts in 8 patients (10%), and wallerian degeneration of the pyramidal tract in 8 (24%) of the 34 patients with posterior capsular or putamenal infarcts on initial MRI. Our data suggest that new, clinically silent infarcts may be at least as common as recurrent strokes in patients with lacunar infarctions.

To determine the clinical usefulness of gadolinium-DPTA-enhanced MRI in identifying recent small, deep infarcts we prospectively studied 91 patients with first-ever stroke and presenting with a lacunar syndrome. In 78 patients (85.7%), plain MRI revealed possibly appropriate infarcts, classified as deep (n = 69), internal borderzone (n = 1), and cortical (n = 8 patients). Enhancement was seen in 38 (80.9%) of 47 patients with only one possibly relevant deep lesion on plain MRI, and in 14 (63.6%) out of 22 patients with multiple lesions. MRI with gadolinium-DPTA facilitates identification of the relevant lesion in patients with presumed lacunar infarcts.

T-lymphocytes are probably involved in the pathogenesis of Guillain-Barré syndrome (GBS). T-helper-1 (Th1) cytokines activate macrophages and induce a delayed type hypersensitivity (DTH) inflammatory response, consistent with the morphology of the demyelination in GBS. Th2 cytokines encourage antibody production and downregulate Th1 responses. To study the Th1/Th2 cytokines in relation to the clinical course of GBS an ELISPOT method for determination of single cells secreting interferon-gamma, IFN-gamma (Th1) or interleukin-4, IL-4 (Th2) was used. We serially investigated antigen-induced cytokine secretion from circulating T-cells stimulated with human peptides from the P0 and P2 proteins in seven patients and compared to results from seven serially investigated healthy controls. Most patients (five of seven) showed IL-4 responses during the plateau- or recovery-phase as compared to controls. One patient with a prolonged disease course, on the other hand, had an IFN-gamma dominated reactivity. We suggest that the IL-4 responses are beneficial in GBS, and may have a role in terminating the disease process in this self-limiting inflammatory disease.

Background and Purpose Little is known about the prognosis and the predictive factors for functional outcome after lacunar infarction. Our aim was to analyze this issue in more detail and with a longer follow-up than in previous reports. Methods Functional outcome was assessed in 81 consecutive patients with a first-ever stroke and clinical and MRI findings compatible with lacunar infarction. We measured impairment (motor, sensory, and cognitive function), disability (Katz’s Index of Activities of Daily Living [ADL] and four instrumental activities), and handicap (Oxford Handicap Scale). The patients were followed up for 3 years. Results During follow-up, 6% of the patients died and 21% had recurrent strokes, mostly new lacunar infarcts. A fast initial recovery was found in most patients. At 1 year, 12% were dependent in personal ADL, which after 3 years had increased to 24%, mostly as a result of the effects of recurrent strokes. In a logistic multivariate regression model, moderate or severe hemiparesis 1 month after stroke onset was the strongest predictor of physical dependence or death at 3 years ( P P Conclusions Functional outcome regarding physical independence was favorable in most patients. Motor impairment and white matter disease were the strongest predictors of a poor functional outcome. Recurrent stroke increased disability and handicap but was not a statistically significant independent risk factor. Measurements of personal ADL alone were insensitive in detecting the consequences of stroke in many patients with preserved self-care ability, who still experienced disability and handicap.

Poststroke depression is a frequent condition and important to treat. The aim of this trial was to study the efficacy and tolerability of sertraline.In 4 Swedish stroke centers, 123 patients (aged 70.7 +/- 9.9 years) were enrolled during the period September 1998 to January 2001 in a randomized, double-blind, placebo-controlled 26-week trial, at a mean of 128 +/- 97 days (range, 3-375 days) after stroke, if they fulfilled DSM-IV criteria of major depressive episode (N = 76) or minor depressive disorder (N = 47). The primary efficacy variable was a change in depression assessed by the Montgomery-Asberg Depression Rating Scale. The Emotional Distress Scale (EDS) was administered and the occurrence of emotionalism and quality of life (QoL) were assessed, as well as neurologic recovery. Efficacy analyses were intention-to-treat, short-term (week 6) and long-term (week 26).Of the 123 patients, 62 were treated with sertraline (50-100 mg/day) and 61 with placebo. Both groups improved substantially, with no differences between the treatments, either for major depressive episode or minor depressive disorder, or for short- or long-term antidepressant effect and neurologic outcome. EDS revealed a better outcome with sertraline at week 6 (p.05). At week 26, the improvement in QoL was better in sertraline patients (p.05) and there was a trend for emotionalism (p = .07). No serious side effects were seen.Poststroke depression as measured by a conventional depression rating scale improved over time irrespective of treatment. Positive effects specific to sertraline were identified in emotional distress, emotionalism, and QoL. The study indicates that poststroke emotional reactions comprise depression and other domains susceptible to pharmacologic therapy.