Changes in lipid metabolism track with the progression of neurofibrillary pathology in tauopathies.

BACKGROUND: Accumulation of tau leads to neuroinflammation and neuronal cell death in tauopathies, including Alzheimer's disease. As the disease progresses, there is a decline in brain energy metabolism. However, the role of tau protein in regulating lipid metabolism remains less characterized and poorly understood. METHODS: We used a transgenic rat model for tauopathy to reveal metabolic alterations induced by neurofibrillary pathology. Transgenic rats express a tau fragment truncated at the N- and C-terminals. For phenotypic profiling, we performed targeted metabolomic and lipidomic analysis of brain tissue, CSF, and plasma, based on the LC-MS platform. To monitor disease progression, we employed samples from transgenic and control rats aged 4, 6, 8, 10, 12, and 14 months. To study neuron-glia interplay in lipidome changes induced by pathological tau we used well well-established multicomponent cell model system. Univariate and multivariate statistical approaches were used for data evaluation. RESULTS: We showed that tau has an important role in the deregulation of lipid metabolism. In the lipidomic study, pathological tau was associated with higher production of lipids participating in protein fibrillization, membrane reorganization, and inflammation. Interestingly, significant changes have been found in the early stages of tauopathy before the formation of high-molecular-weight tau aggregates and neurofibrillary pathology. Increased secretion of pathological tau protein in vivo and in vitro induced upregulated production of phospholipids and sphingolipids and accumulation of lipid droplets in microglia. We also found that this process depended on the amount of extracellular tau. During the later stages of tauopathy, we found a connection between the transition of tau into an insoluble fraction and changes in brain metabolism. CONCLUSION: Our results revealed that lipid metabolism is significantly affected during different stages of tau pathology. Thus, our results demonstrate that the dysregulation of lipid composition by pathological tau disrupts the microenvironment, further contributing to the propagation of pathology.

Cerebrospinal fluid and blood serum biomarkers in neurodegenerative proteinopathies: A prospective, open, cross-correlation study.

Neurodegenerative diseases are a broad heterogeneous group affecting the nervous system. They are characterized, from a pathophysiological perspective, by the selective involvement of a subpopulation of nerve cells with a consequent clinical picture of a disease. Clinical diagnoses of neurodegenerative diseases are quite challenging and often not completely accurate because of their marked heterogeneity and frequently overlapping clinical pictures. Efforts are being made to define sufficiently specific and sensitive markers for individual neurodegenerative diseases or groups of diseases in order to increase the accuracy and speed of clinical diagnosis. Thus said, this present research aimed to identify biomarkers in the cerebrospinal fluid (CSF) and serum (α-synuclein [α-syn], tau protein [t-tau], phosphorylated tau protein [p-tau], ß-amyloid [Aß], clusterin, chromogranin A [chromogrA], cystatin C [cyst C], neurofilament heavy chains [NFH], phosphorylated form of neurofilament heavy chains [pNF-H], and ratio of tau protein/amyloid beta [Ind tau/Aß]) that could help in the differential diagnosis and differentiation of the defined groups of α-synucleinopathies and four-repeat (4R-) tauopathies characterized by tau protein isoforms with four microtubule-binding domains. In this study, we analyzed a cohort of 229 patients divided into four groups: (1) Parkinson's disease (PD) + dementia with Lewy bodies (DLB) (n = 82), (2) multiple system atrophy (MSA) (n = 25), (3) progressive supranuclear palsy (PSP) + corticobasal syndrome (CBS) (n = 30), and (4) healthy controls (HC) (n = 92). We also focused on analyzing the biomarkers in relation to each other with the intention of determining whether they are useful in distinguishing among individual proteinopathies. Our results indicate that the proposed set of biomarkers, when evaluated in CSF, is likely to be useful for the differential diagnosis of MSA versus 4RT. However, these biomarkers do not seem to provide any useful diagnostic information when assessed in blood serum.

Temperature sensation in Parkinson's disease measured by quantitative sensory testing: a single-center, case-control study.

BACKGROUND: The pathophysiology of abnormal temperature sensation in Parkinson's disease (PD) remains unclear. Abnormal thermal detection does not seem to depend on the dopaminergic deficit, suggesting that other systems play a role in these changes, probably both central and peripheral. METHODS: We measured thermal detection thresholds (TDT) using quantitative sensory testing (QST) in 28 patients with PD and compared them with 15 healthy controls. RESULTS: Of 28 patients, 21% had increased TDT according to the normative data. TDT were higher on the dominant side. No correlation between TDT and disease duration, severity of motor impairment, and dopaminergic therapy was observed. 50% of the patients had difficulty differentiating between warm and cold stimuli, as TDT were within the normal range in most of these patients. CONCLUSIONS: Twenty-one percent of the patients in our study had increased TDT according to the normative data. Abnormal thermal detection was more pronounced on the dominant side. Abnormal differentiation between the thermal stimuli suggest impaired central processing of thermal information.

Pathogenesis of Alzheimer's disease: Involvement of the choroid plexus.

The choroid plexus (ChP) produces and is bathed in the cerebrospinal fluid (CSF), which in aging and Alzheimer's disease (AD) shows extensive proteomic alterations including evidence of inflammation. Considering inflammation hampers functions of the involved tissues, the CSF abnormalities reported in these conditions are suggestive of ChP injury. Indeed, several studies document ChP damage in aging and AD, which nevertheless remains to be systematically characterized. We here report that the changes elicited in the CSF by AD are consistent with a perturbed aging process and accompanied by aberrant accumulation of inflammatory signals and metabolically active proteins in the ChP. Magnetic resonance imaging (MRI) imaging shows that these molecular aberrancies correspond to significant remodeling of ChP in AD, which correlates with aging and cognitive decline. Collectively, our preliminary post-mortem and in vivo findings reveal a repertoire of ChP pathologies indicative of its dysfunction and involvement in the pathogenesis of AD. HIGHLIGHTS: Cerebrospinal fluid changes associated with aging are perturbed in Alzheimer's disease Paradoxically, in Alzheimer's disease, the choroid plexus exhibits increased cytokine levels without evidence of inflammatory activation or infiltrates In Alzheimer's disease, increased choroid plexus volumes correlate with age and cognitive performance.

Contemporary clinical neurophysiology applications in dystonia.

The complex phenomenological understanding of dystonia has transcended from the clinics to genetics, imaging and neurophysiology. One way in which electrophysiology will impact into the clinics are cases wherein a dystonic clinical presentation may not be typical or a "forme fruste" of the disorder. Indeed, the physiological imprints of dystonia are present regardless of its clinical manifestation. Underpinnings in the understanding of dystonia span from the peripheral, segmental and suprasegmental levels to the cortex, and various electrophysiological tests have been applied in the course of time to elucidate the origin of dystonia pathophysiology. While loss of inhibition remains to be the key finding in this regard, intricacies and variabilities exist, thus leading to a notion that perhaps dystonia should best be gleaned as network disorder. Interestingly, the complex process has now spanned towards the understanding in terms of networks related to the cerebellar circuitry and the neuroplasticity. What is evolving towards a better and cohesive view will be neurophysiology attributes combined with structural dynamic imaging. Such a sound approach will significantly lead to better therapeutic modalities in the future.

Consensus guidelines for botulinum toxin therapy: general algorithms and dosing tables for dystonia and spasticity.

Botulinum toxin (BT) therapy is a complex and highly individualised therapy defined by treatment algorithms and injection schemes describing its target muscles and their dosing. Various consensus guidelines have tried to standardise and to improve BT therapy. We wanted to update and improve consensus guidelines by: (1) Acknowledging recent advances of treatment algorithms. (2) Basing dosing tables on statistical analyses of real-life treatment data of 1831 BT injections in 36 different target muscles in 420 dystonia patients and 1593 BT injections in 31 different target muscles in 240 spasticity patients. (3) Providing more detailed dosing data including typical doses, dose variabilities, and dosing limits. (4) Including total doses and target muscle selections for typical clinical entities thus adapting dosing to different aetiologies and pathophysiologies. (5) In addition, providing a brief and concise review of the clinical entity treated together with general principles of its BT therapy. For this, we collaborated with IAB-Interdisciplinary Working Group for Movement Disorders which invited an international panel of experts for the support.

Arterial Hypertension and Risk of Recurrent Event in Young Ischemic Stroke Patients.

INTRODUCTION: In young patients, the cause of ischemic stroke (IS) remains often cryptogenic despite presence of traditional vascular risk factors (VRFs). Since arterial hypertension (AH) is considered the most important one, we aimed to evaluate the impact of AH and blood pressure (BP) levels after discharge on risk of recurrent IS (RIS) in young patients. METHODS: The study set consisted of acute IS patients < 50 years of age enrolled in the prospective Heart and Ischemic STrOke Relationship studY registered on ClinicalTrials.gov (NCT01541163). Cause of IS was assessed according to the ASCOD classification. RESULTS: Out of 319 enrolled patients <50 years of age (179 males, mean age 41.1 ± 7.8 years), AH was present in 120 (37.6%) of them. No difference was found in the rates of etiological subtypes of IS between patients with and without AH. Patients with AH were older, had more VRF, used more frequently antiplatelets prior IS, and had more RIS (10 vs. 1%, p = 0.002) during a follow-up (FUP) with median of 25 months. Multivariate logistic regression stepwise model showed the prior use of antiplatelets as only predictor of RIS (p = 0.011, OR: 6.125; 95% CI: 1.510-24.837). Patients with elevated BP levels on BP Holter 1 month after discharge did not have increased rate of RIS during FUP (3.8 vs. 1.7%, p = 1.000). CONCLUSION: AH occurred in 37.6% of young IS patients. Patients with AH had more frequently RIS. Prior use of antiplatelets was found only predictor of RIS in young IS patients with AH.

Cerebrospinal Fluid Levels of 5-Hydroxyindoleacetic Acid in Parkinson's Disease and Atypical Parkinsonian Syndromes.

BACKGROUND: Various cerebrospinal fluid (CSF) biomarkers are studied in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS). Several studies found reduced 5-hydroxyindoleacetic acid (5-HIAA), the main serotonin metabolite, in PD. There is little evidence regarding its levels in APS. METHODS: We measured 5-HIAA in the CSF of 90 PD patients, 16 MSA patients, 26 progressive supranuclear palsy (PSP) patients, 11 corticobasal syndrome (CBS) patients, and 31 controls. We also compared the values in depressed and nondepressed patients. RESULTS: There was a statistically significant difference in CSF 5-HIAA in PD and MSA compared to the control group (median in PD 15.8 µg/L, in MSA 13.6 µg/L vs. 24.3 µg/L in controls; p = 0.0008 in PD, p = 0.006 in MSA). There was no statistically significant difference in CSF 5-HIAA in PSP and CBS compared to the control group (median in PSP 22.7 µg/L, in CBS 18.7 µg/L vs. 24.3 µg/L in controls; p = 1 in both PSP and CBS). CSF 5-HIAA levels were lower in PD patients with depression compared to PD patients without depression (median 8.34 vs. 18.48, p < 0.0001). CONCLUSIONS: CSF 5-HIAA is decreased in PD and MSA. The CSF 5-HIAA levels in PSP and CBS did not differ from those of the control group. There was a tendency toward lower CSF 5-HIAA in MSA than in PD; however, the results did not reach statistical significance. These results may be explained by more severe damage of the serotonergic system in synucleinopathies (PD and MSA) than in tauopathies (PSP and CBS).

Cytokinin Plant Hormones Have Neuroprotective Activity in In Vitro Models of Parkinson's Disease.

Cytokinins are adenine-based phytohormones that regulate key processes in plants, such as cell division and differentiation, root and shoot growth, apical dominance, branching, and seed germination. In preliminary studies, they have also shown protective activities against human neurodegenerative diseases. To extend knowledge of the protection (protective activity) they offer, we investigated activities of natural cytokinins against salsolinol (SAL)-induced toxicity (a Parkinson's disease model) and glutamate (Glu)-induced death of neuron-like dopaminergic SH-SY5Y cells. We found that kinetin-3-glucoside, cis-zeatin riboside, and N6-isopentenyladenosine were active in the SAL-induced PD model. In addition, trans-, cis-zeatin, and kinetin along with the iron chelator deferoxamine (DFO) and the necroptosis inhibitor necrostatin 1 (NEC-1) significantly reduced cell death rates in the Glu-induced model. Lactate dehydrogenase assays revealed that the cytokinins provided lower neuroprotective activity than DFO and NEC-1. Moreover, they reduced apoptotic caspase-3/7 activities less strongly than DFO. However, the cytokinins had very similar effects to DFO and NEC-1 on superoxide radical production. Overall, they showed protective activity in the SAL-induced model of parkinsonian neuronal cell death and Glu-induced model of oxidative damage mainly by reduction of oxidative stress.

Socioeconomic status and lifestyle in young ischaemic stroke patients: a possible relationship to stroke recovery and risk of recurrent event.

OBJECTIVES: Socioeconomic status (SES) and lifestyle have impact on recovery after ischaemic stroke (IS) and on risk of recurrent ischaemic stroke (RIS) in elderly patients. With regard to currently available limited data on young people, we aimed to assess SES and parameters of lifestyle and evaluate their relationship to stroke recovery and risk of RIS in young patients. METHODS: We analysed consecutive young IS patients < 50 years enrolled in the prospective HISTORY (Heart and Ischaemic STrOke Relationship studY) study registered on ClinicalTrials.gov (NCT01541163). Data were acquired from structured a self-evaluating multiple-choice questionnaire. Clinical outcome was assessed using the Modified Rankin Scale (MRS) after 3 months with score 0-1 for excellent outcome. RESULTS: Data were obtained from 297 (163 males, mean age 39.6 ± 7.8 years) young patients. Patients with MRS 0-1 (237, 79.8%) did not differ in SES except university education (21.1 vs. 3.3%; p = 0.001), less smoked (16.5 vs. 58.3%; p < 0.001), more of them did regular sport activities (79.1 vs. 51.6%; p = 0.02) and passed regular preventive medical checks (45.6 vs. 24.2%; p = 0.01). Twelve (4%) patients suffered from RIS during a follow-up with median of 25 months. They did not differ in SES but had higher body mass index (31.6 vs. 26.7; p = 0.007), reported less regular sport activities (16.7 vs. 73.0%; p < 0.001) and less regular medical checks (8.3 vs. 40.0%; p = 0.001). CONCLUSION: In young patients, SES had no relationship to clinical outcome after IS and to risk of RIS except education level. Some parameters of health lifestyle were presented more in patients with excellent outcome and without RIS during the follow-up.

Botulinum neurotoxin injections for muscle-based (dystonia and spasticity) and non-muscle-based (neuropathic pain) pain disorders: a meta-analytic study.

Apart from the known efficacy of Botulinum Neurotoxin Type A (BoNT/A) in hyperactive striated and smooth muscles, different pain states have become potential targets of toxin effects. This present study determined the comparative toxin effectiveness in pain reduction among those patients injected with BoNT/A in muscle-based and in non-muscle-based conditions. Randomized controlled trials (RCTs) on the effect of BoNT/A on selected pain conditions were included. The conditions were spasticity and dystonia for muscle-based pain. For non-muscle-based pain, conditions included were painful diabetic neuropathy (PDN), post-herpetic neuralgia (PHN), trigeminal neuralgia (TN), complex regional pain syndrome (CRPS), and spinal cord injury (SCI). In view of possibly differing pathophysiology, myofascial pain, temporomandibular joint (TMJ), other joint or tendon pains, cervicogenic and lumbar pains, migraine and visceral pain syndromes were excluded. Standardized mean difference was used as the effect measure and computed with STATA. 25 RCTs were analyzed. Pooled estimates showed significantly lower pain score in the Treatment group (z = 5.23, p < 0.01, 95% CI = - 0.75, - 0.34). Subgroup analyses showed that BoNT/A significantly reduced both muscle-based (z = 3.78, p < 0.01, 95% CI = - 0.72, - 0.23) and non-muscle-based (z = 3.37, p = 0.001, 95% CI = - 1.00, - 0.27) pain. Meta-regression using four covariates namely dosage, route, frequency and duration was done which revealed that dosage significantly affects standardized mean differences, while the other three covariates were insignificant. The joint F-test was found to be insignificant (p value = 0.1182). The application of the model with these covariates does not significantly explain the derived heterogeneity of standardized mean differences. In conclusion, BoNT/A can be effectively used in muscle-based and non-muscle-based pain disorders. We detected no difference between the presence and magnitude of pain relief favoring muscle-based compared to non-muscle-based pain. Thus, we cannot say whether or not there might be independent mechanisms of toxin-induced pain relief for pain generated from either muscle or nerve hyperactivity.

Young cryptogenic ischemic stroke: A descriptive analysis of clinical and laboratory characteristics, outcomes and stroke recurrence.

BACKGROUND AND PURPOSE: Ischemic strokes (IS) occur also in young adults and despite an extensive work-up the cause of IS remains very often cryptogenic. Thus, effectiveness of secondary prevention may be unclear. We aimed to analyze a relationship among vascular risk factors (VRF), clinical and laboratory parameters, outcomes and recurrent IS (RIS) in young cryptogenic IS (CIS) patients. SUBJECTS AND METHODS: The study set consisted of young acute IS patients < 50 years enrolled in the prospective HISTORY (Heart and Ischemic STrOke Relationship studY) study registered on ClinicalTrials.gov (NCT01541163). All analyzed patients underwent transesophageal echocardiography, 24-h and 3-week ECG-Holter to assess cause of IS according to the ASCOD classification. Recurrent IS (RIS) was recorded during a follow-up (FUP). RESULTS: Out of 294 young enrolled patients, 208 (70.7%, 113 males, mean age 41.6 ± 7.2 years) were identified as cryptogenic. Hyperlipidemia (43.3%), smoking (40.6%) and arterial hypertension (37.0%) were the most frequent VRF. RIS occurred in 7 (3.4%) patients during a mean time of FUP 19 ± 23 months. One-year risk of RIS was 3.4% (95%CI: 1.4-6.8%). Patients with RIS were older (47.4 vs. 41.1 years, p = 0.007) and more often obese (71.4 vs. 19.7%, p = 0.006), and did not differ in any of other analyzed parameters and VRF. Multivariate logistic regression analysis showed obesity (OR: 9.527; 95%CI: 1.777-51.1) and the previous use of antiplatelets (OR: 15.68; 95%CI: 2.430-101.2) as predictors of recurrent IS. CONCLUSION: Despite a higher presence of VRF in young CIS patients, the risk of RIS was very low. Obesity and previous use of antiplatelet therapy were found the only predictors of RIS.

Low Levels of Glycemia within the First 48 Hours after Mechanical Thrombectomy for Acute Ischemic Stroke May be Associated with Better Clinical Outcome.

INTRODUCTION: Many different factors may have an impact on clinical outcome after mechanical thrombectomy (MT) for acute ischemic stroke (AIS). We aimed to investigate levels of serum glycemia (GLY) within the first 48 hours after MT. SUBJECTS AND METHODS: Consecutive AIS patients were enrolled in the retrospective bi-center study. Neurological deficit was assessed with National Institutes of Health Stroke Scale (NIHSS) and functional outcome after 3 months with modified Rankin scale with a score 0-2 for good outcome. Presence of symptomatic intracerebral hemorrhage was assessed according to the SITS- MOST criteria. RESULTS: In total, 868 patients (442 males, mean age 69.7 ± 12.2 years) with a median of admission NIHSS 17 points were enrolled in the study and 253 (29.1%) of them were diabetics. Recanalization was reached in 758 (87.3%) patients. Patients with good outcome (412, 47.5%) had lower median of GLY (6.5 versus 7.4 mmol/L, P < .0001) within the first 48 hours after MT. Similar results were found also in diabetics (8.1 versus 9.6 mmol/L, P < .0001) and in patients with achieved recanalization (6.5 versus 7.5 mmol/L, P < .0001). Multivariate regression analysis with adjustment for potential confounders showed median of GLY (P = .0001, odds ratio: 0.830, 95% confidence interval: 0.755-0.913) as a predictor of good outcome after MT. CONCLUSION: Lower levels of GLY within the first 48 hours after MT may be associated with better functional outcome after 3 months.

Changes in sensorimotor network activation after botulinum toxin type A injections in patients with cervical dystonia: a functional MRI study.

Botulinum toxin type A (BoNT) is considered an effective therapeutic option in cervical dystonia (CD). The pathophysiology of CD and other focal dystonias has not yet been fully explained. Results from neurophysiological and imaging studies suggest a significant involvement of the basal ganglia and thalamus, and functional abnormalities in premotor and primary sensorimotor cortical areas are considered a crucial factor in the development of focal dystonias. Twelve BoNT-naïve patients with CD were examined with functional MRI during a skilled hand motor task; the examination was repeated 4 weeks after the first BoNT injection to the dystonic neck muscles. Twelve age- and gender-matched healthy controls were examined using the same functional MRI paradigm without BoNT injection. In BoNT-naïve patients with CD, BoNT treatment was associated with a significant increase of activation in finger movement-induced fMRI activation of several brain areas, especially in the bilateral primary and secondary somatosensory cortex, bilateral superior and inferior parietal lobule, bilateral SMA and premotor cortex, predominantly contralateral primary motor cortex, bilateral anterior cingulate cortex, ipsilateral thalamus, insula, putamen, and in the central part of cerebellum, close to the vermis. The results of the study support observations that the BoNT effect may have a correlate in the central nervous system level, and this effect may not be limited to cortical and subcortical representations of the treated muscles. The results show that abnormalities in sensorimotor activation extend beyond circuits controlling the affected body parts in CD even the first BoNT injection is associated with changes in sensorimotor activation. The differences in activation between patients with CD after treatment and healthy controls at baseline were no longer present.

Longitudinal brain activation changes related to electrophysiological findings in patients with cervical spondylotic myelopathy before and after spinal cord decompression: an fMRI study.

BACKGROUND: Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord dysfunction, potentially leading to severe disability. Abnormal cervical spine magnetic resonance imaging (MRI) and motor evoked potentials (MEPs) are independent predictors of disease progression. Abnormal MRI is accompanied by various activation changes in functional brain MRI (fMRI), whereas preoperative and postoperative fMRI adaptations associated with abnormal preoperative MEP remain unknown. METHODS: Twenty patients (9 males, average age 56.6) with evidence of spinal cord compression on MRI and clinical signs of mild CSM were included. Participants were classified according to their preoperative MEP and underwent three brain fMRI examinations: before surgery, 6, and 12 months after surgery while performing repeated extension-flexion of each wrist. RESULTS: Functional MRI activation was compared between two subsets of patients, with normal and clearly abnormal MEP (right wrist: 8 vs. 8; left wrist: 7 vs. 9). At baseline, abnormal MEPs were associated with hyperactivation in the cerebellum. At the first follow-up, further hyperactivations emerged in the contralateral sensorimotor cortices and persisted for 1 year. In normal baseline MEP, activation mostly decreased in the ipsilateral sensorimotor cortex postoperatively. The ipsilateral sensorimotor activation after 1-year follow-up correlated with baseline MEP. CONCLUSIONS: Abnormal corticospinal MEP findings in cervical spondylotic myelopathy were associated with differences in brain activation, which further increased after spinal cord decompression and did not resolve within 12-month follow-up. In summary, surgery may come too late for those patients with abnormal MEP to recover completely despite their mild clinical signs and symptoms.

Motion and emotion: anxiety-axial connections in Parkinson's disease.

Anxiety is a serious and frequent complication in Parkinson's disease (PD) that significantly affects the quality of life of patients. Multiple neuroanatomical, experimental, and clinical studies suggest its close association with axial disturbances. However, whether this relation applies for PD patients (commonly suffering from axial difficulties, such as balance and gait disturbance) has not been properly tested yet. The purpose of this study was to determine whether PD patients suffering from axial symptoms have higher levels of anxiety than others and to identify other factors associated with anxiety-axial connections. In this questionnaire study, 212 patients with PD were assessed by standardized scales, such as Hamilton Anxiety Scale, Montgomery-Asberg Depression Rating Scale, Montreal Cognitive Assessment, examining their mood and cognitive status. These data were correlated to dominant motor symptoms of these patients, such as tremor, rigidity, bradykinesia, and axial symptoms. Unlike other motor symptoms, only axial symptoms showed to be significantly related to higher levels of anxiety. The patients suffering from anxiety and axial problems have also shown significantly higher depression levels. Axial disturbances are related to higher anxiety levels in PD patients. It is crucial to pay high attention to symptoms of anxiety in patients having postural instability or gait disorder. Further clinical studies are desirable to investigate new, practical implications of anxiety-axial connection to provide complex management options of these serious symptoms.

Effect of Primary Preventive Examination with Cardiorespiratory Fitness Test.

OBJECTIVE: The aim of this study was to explore the potential of free comprehensive primary preventive examination (CPPE) combined with cardiorespiratory fitness (CRF) test in terms of its attractiveness for general population and moreover to evaluate the induced behavioural changes. The main focus was on physical activity behaviour (PA). METHODS: In 2009-2013, 250 people (100 men, 150 women) aged 18-65 years were examined. CPPE included assessment of health status and lifestyle, CRF test and individualized counselling. Expectations, reasons and motivations for participating were recorded. The sample was evaluated in terms of age, gender, lifestyle, body mass index, body fat percentage, CRF, and health characteristics. Evaluation according to subjective benefits, perceived effects on health and lifestyle was performed after six months using electronic feedback questionnaires (FQ). Comparison was made within groups formed according to the reported increase in PA. RESULTS: People aged 18-39 years accounted for 72.8% of the sample; mean age 34.4±11.0 years; 40.0% were men. Behavioural and health risks were lower in comparison with the general Czech population, but at least 1 of 5 assessed risk factors was present in 88.8% (low fruit and vegetable consumption 74.8%, low physical activity level (PAL) 45.6%, smoking 19.6%, risky alcohol use 18.8%, and stress load 10.4%). The most represented category of CRF was "endurance-trained" (both genders). CPPE was perceived as a source of information concerning health, CRF and lifestyle. 40.0% of men and 30.7% of women were focused on improvement in CRF. The response rate of FQ was 75.6%. Individuals with low PAL and low CRF provided feedback less often (p<0.05). In terms of perceived effect, 84.1% of the respondents implemented some kind of behavioural change; 60.9% reported increase in PA, but only 38.1% reported maintaining improvement in PA after 6 months. A higher proportion of reported lasting changes in PA occurred in subjects who were overweight/obese and in those with low CRF. Participants with low PAL and higher number of lifestyle risks more likely increased their PA only temporarily. Improvement in PA was associated with reported changes in diet (p<0.001). In the group of respondents there was an increase in self-perceived PA (SPA) compared to the baseline (p=0.001). Moreover, individuals who reported increase in PA showed improvement in subjectively perceived health. CONCLUSION: The testing of CRF appears to be a promising motivating factor for going through the intervention, especially for younger people and men. CPPE is effective at the individual level in terms of providing information and initiating behavioural changes in PA. However, this type of intervention is less attractive and less effective for individuals with a higher behavioural risk profile.

Randomized, placebo-controlled trial of incobotulinumtoxina for upper-limb post-stroke spasticity.

INTRODUCTION: Efficacy and safety of incobotulinumtoxinA in post-stroke upper-limb spasticity were studied. METHODS: Subjects randomized 2:1 to incobotulinumtoxinA (fixed dose 400 U) or placebo, with fixed doses for the primary target clinical pattern (PTCP; flexed elbow, 200 U; flexed wrist, 150 U; clenched fist, 100 U). Doses for non-primary patterns were flexible within predefined ranges. RESULTS: At week 4, incobotulinumtoxinA led to larger improvements in PTCP Ashworth scale (AS) scores than placebo [least-squares mean change ± standard error: -0.9 ± 0.06 (n = 171) vs. -0.5 ± 0.08 (n = 88); P < 0.001], and more subjects were PTCP AS responders (≥1-point improvement) with incobotulinumtoxinA (69.6%) than with placebo (37.5%; P < 0.001). Investigator's Global Impression of Change confirmed superiority of incobotulinumtoxinA vs. placebo (P = 0.003). IncobotulinumtoxinA was associated with functional improvements, as demonstrated in responder rates for Disability Assessment Scale principal target at week 4 (P = 0.007). Adverse events were mainly mild/moderate, and were reported by 22.4% (incobotulinumtoxinA) and 16.8% (placebo) of subjects. CONCLUSIONS: IncobotulinumtoxinA significantly improved upper-limb spasticity and associated disability, and was well-tolerated.

Strategies for treatment of dystonia.

Treatment of dystonias is generally symptomatic. To produce sufficient therapy effects, therefore, frequently a multimodal and interdisciplinary therapeutic approach becomes necessary, combining botulinum toxin therapy, deep brain stimulation, oral antidystonic drugs, adjuvant drugs and rehabilitation therapy including physiotherapy, occupational therapy, re-training, speech therapy, psychotherapy and sociotherapy. This review presents the recommendations of the IAB-Interdisciplinary Working Group for Movement Disorders Special Task Force on Interdisciplinary Treatment of Dystonia. It reviews the different therapeutic modalities and outlines a strategy to adapt them to the dystonia localisation and severity of the individual patient. Hints to emerging and future therapies will be given.

Botulinum toxin treatment of freezing of gait in Parkinson's disease patients as reflected in functional magnetic resonance imaging of leg movement.

BACKGROUND: Freezing of gait (FOG) is a common disabling symptom of (in) Parkinson's disease (PD). The mechanism of FOG is (in) not clearly understood. We investigated the clinical effect and changes of the activity of the sensorimotor system using repeated functional MRI (fMRI) before and after application of botulinum toxin in Parkinson's disease patients with FOG. METHODS: We investigated 20 patients with PD, 10 with FOG and 10 without FOG. PD patients with FOG were treated with intramuscular application of botulinum toxin type A into the tensor fasciae latae muscle bilaterally. The clinical effect of treatment was assessed using FOG questionnaire, "Time up and go" test, UPDRS, Hoehn and Yahr staging, Clinical global impression scale. Activation of the sensorimotor system was studied using BOLD fMRI of the whole brain during repetitive abduction - adduction of each leg interleaved with rest. The clinical (in the FOG group) and imaging (in both groups) examination was repeated after a four-week interval. RESULTS: In the FOG group, the FOG questionnaire has shown a decline of scores after application of botulinum toxin that suggests possible effect of botulinum toxin on freezing of gait. In fMRI results, both groups manifested reduction of the sensorimotor network activated with leg movement, however, the FOG group also showed increased activation in cerebellar vermis and nuclei, in dorsal pons and in medulla after treatment. CONCLUSION: Alleviation of the FOG in PD patients by botulinum toxin seems to be reflected in the functional participation of the cerebellum and its projections as seen by fMRI.