Finnish Brain Research and Rehabilitation Center Neuron

Background: Heat sensitivity is a common feature of multiple sclerosis (MS), and heat has been found to impair MS patients’ physical and cognitive functioning. There is, however, no simple and specific measurement tool to evaluate the possible effects of heat on these functions. Objectives: The aim of this study was to evaluate the compatibility of the multiple sclerosis functional composite (MSFC) to demonstrate the effects of heat on functioning in patients with MS. Patients and Methods: A total of 22 heat-sensitive MS patients and 19 healthy controls (HCs) were considered for the analysis. Moderate heat exposure took place in a Finnish sauna. Functioning was measured with the MSFC, which consists of two physical (the Nine Hole Peg test and the 25-foot timed walk test) and one cognitive (the PASAT-3) measure, before, during and one hour after the heat exposure. Results: In the MS group the average MSFC scores were -0.48 (SD 0.79) at baseline, -0.99 (SD 1.97) during heat exposure and -0.68 (SD 1.58) after a one-hour delay. The average MSFC scores of the HC group were 0.58 (SD 0.42) at baseline, 0.66 (SD 0.43) during heat exposure and 0.68 (SD 0.41) after a one-hour delay. The MS group had significantly lower MSFC scores than the HC group (P = 0.01). The MS patients’ score deteriorated during the heat exposure, whereas that of the controls did not (P = 0.00). Conclusions: The results suggest that the MSFC could be used as a simple tool to detect the negative effects of heat in patients with MS.

Background. Evaluation of treatment effects on walking requires appropriate and responsive outcome measures. Objectives. To determine responsiveness of 5 walking measures and provide reference values for clinically meaningful improvements, according to disability level, in persons with multiple sclerosis (pwMS). Methods. Walking tests were measured pre- and postrehabilitation in 290 pwMS from 17 European centers. Combined anchor- and distribution-based methods determined responsiveness of objective short and long walking capacity tests (Timed 25-Foot Walk [T25FW] and 2- and 6-Minute Walk Tests [2MWT and 6MWT] and of the patient-reported Multiple Sclerosis Walking Scale–12 [MSWS-12]). A global rating of change scale, from patients’ and therapists’ perspective, was used as external criteria to determine the area under the receiver operating characteristic curve (AUC), minimally important change (MIC), and smallest real change (SRC). Patients were stratified into disability subgroups (Expanded Disability Status Scale score ≤4 [n = 98], >4 [n = 186]). Results. MSWS-12, 2MWT, and 6MWT were more responsive (AUC 0.64-0.73) than T25FW (0.50-0.63), especially in moderate to severely disabled pwMS. Clinically meaningful changes (MICs) from patient and therapist perspective were −10.4 and −11.4 for MSWS-12 (P < .01), 9.6 m and 6.8 m for 2MWT (P < .05), and 21.6 m (P < .05) and 9.1 m (P = .3) for 6MWT. In subgroups, MIC was significant from patient perspective for 2MWT (10.8 m) and from therapist perspective for MSWS-12 (−10.7) in mildly disabled pwMS. In moderate to severely disabled pwMS, MIC was significant for MSWS-12 (−14.1 and −11.9). Conclusions. Long walking tests and patient-reported MSWS-12 were more appropriate than short walking tests in detecting clinically meaningful improvement after physical rehabilitation, particularly the MSWS-12 for moderate to severely disabled pwMS.

The aim of this study was to examine the association between hangover and the risk of stroke. A population-based sample of men with an average follow-up of 15.7 years. 2466 men with no history of stroke at baseline participated. Two hundred and six strokes occurred, of which 167 were ischemic strokes. The age-adjusted, relative risk (RR) for any stroke among men with ≥1 hangover per year was 2.33-fold (95% confidence interval (CI), 1.19-4.56; P = 0.013) relative to men without hangover, and 2.99-fold (95% CI, 1.52-5.86; P = 0.001) for ischemic stroke, respectively. After adjustment for age, smoking, high density lipoprotein (HDL)-cholesterol, LDL-cholesterol, BMI, SBP, myocardial ischemia during exercise, symptomatic coronary heart disease (CHD) and CHD in family, C-reactive protein, diabetes, and total alcohol consumption, the RR for any stroke was 1.94-fold (95% CI, 0.95-3.96; P = 0.070) and 2.58-fold (95% CI, 1.24-5.36; P = 0.011) for ischemic stroke among men with hangovers. Additional adjustment of atrial fibrillation and cardiac failure and risk was 2.45-fold (95% CI, 1.18-5.12; P = 0.017) for ischemic strokes. This study shows that at least one hangover a year is related to an increased risk of ischemic stroke in men.

Stroke remains one of the main causes of death and disability worldwide. The aging of the population is likely to result in a dramatic increase in the burden of stroke. Thus, it is not surprising that the pharmaceutical industry has invested much money in the development of pharmacotherapies for ischemic stroke. Promising experimental data, however, have almost consistently failed to produce a clinically effective neuroprotective or neurorestorative drug. Only intravenous recombinant tissue plasminogen activator (rtPA) has been approved for the treatment of acute ischemic stroke. Many pharmaceutical companies have scaled down their stroke programs and despite the unmet need, activity in the field is almost frozen. Trafermin, a recombinant form of human basic fibroblast growth factor (bFGF), is a good example of a translational failure in neuroprotection. However, trafermin may also promote neuronal plasticity after cerebral insults. Thus, clinical trials with trafermin in stroke are warranted but should be based on neuronal restoration rather than acute neuroprotection.

Valid experimental models and behavioral tests are indispensable for the development of therapies for stroke. The translational failure with neuroprotective drugs has forced us to look for alternative approaches. Restorative therapies aiming to facilitate the recovery process by pharmacotherapy or cell-based therapy have emerged as promising options. Here we describe the most common stroke models used in cell-based therapy studies with particular emphasis on their inherent complications, which may affect behavioral outcome. Loss of body weight, stress, hyperthermia, immunodepression, and infections particularly after severe transient middle cerebral artery occlusion (filament model) are recognized as possible confounders to impair performance in certain behavioral tasks and bias the treatment effects. Inherent limitations of stroke models should be carefully considered when planning experiments to ensure translation of behavioral data to the clinic.

Cerebral blood flow (CBF) is disrupted after focal ischemia in rats. We examined long-term hemodynamic and cerebrovascular changes in the rat thalamus after focal cerebral ischemia. Cerebral blood flow quantified by arterial spin labeling magnetic resonance imaging was decreased in the ipsilateral and contralateral thalamus 2 days after cerebral ischemia. Partial thalamic CBF recovery occurred by day 7, then the ipsilateral thalamus was chronically hyperperfused at 30 days and 3 months compared with its contralateral side. This contrasted with permanent hypoperfusion in the ipsilateral cortex. Angiogenesis was indicated by endothelial cell (RECA-1) immunohistochemistry that showed increased blood vessel branching in the ipsilateral thalamus at the end of the 3-month follow-up. Only transient thalamic IgG extravasation was observed, indicating that the blood-brain barrier was intact after day 2. Angiogenesis was preceded by transiently altered expression levels of cadherin family adhesion molecules, cadherin-7, protocadherin-1, and protocadherin-17. In conclusion, thalamic pathology after focal cerebral ischemia involved long-term hemodynamic changes and angiogenesis preceded by altered expression of vascular adhesion factors. Postischemic angiogenesis in the thalamus represents a novel type of remote plasticity, which may support removal of necrotic brain tissue and aid functional recovery.

It is well known that increasing age is the strongest risk factor of stroke. Therefore, it has been a common belief in many countries including Finland that the numbers of stroke patients will increase considerably during the next two decades because the population is rapidly ageing. The FINMONICA and FINSTROKE registers operated in Finland in the Kuopio area and city of Turku from 1983 to 1997. The results showed that the incidence, mortality and case fatality of stroke declined significantly during that period. Importantly, it was established that the trends in incidence and mortality were also declining among the elderly (>74 years). We used these results to create a model for the entire country. The model was based on the trends present in these registers from Turku and Kuopio area and age-specific population projections up to the year 2030 that were obtained from Statistics Finland. In the year 2000, the number of new first stroke cases was estimated to be 11 500. If the declining trend were to level off totally after the year 2000, the number of new strokes would be 20 100 in the year 2030 due to the ageing of the population. It would be 12 100 if the trend continued as favourable as during the years 1983-1997. Ageing of the population will not inevitably increase the burden of stroke in Finland if the present declining trends are maintained, but the annual number of cases will almost double if the incidence remains at the level of the year 2000.

We present an advanced method for feature extraction and cluster analysis of surface electromyograms (EMG) and acceleration signals in Parkinson's disease (PD). In the method, 12 different EMG and acceleration signal features are extracted and used to form high-dimensional feature vectors. The dimensionality of these vectors is then reduced by using the principal component approach. Finally, the cluster analysis of feature vectors is performed in a low-dimensional eigenspace. The method was tested with EMG and acceleration data of 42 patients with PD and 59 healthy controls. The obtained discrimination between patients and controls was promising. According to clustering results, one cluster contained 90% of the healthy controls and two other clusters 76% of the patients. Seven patients with severe motor dysfunctions were distinguished in one of the patient clusters. In the future, the clinical value of the method should be further evaluated.