Agnes Floel

Charité Universitätsmedizin Berlin, Berlin, Land Berlin, Germany

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Publications (31)188.54 Total impact

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    ABSTRACT: Therapy guidelines recommend speech and language therapy (SLT) as the "gold standard" for aphasia treatment. Treatment intensity (i.e., >=5 hours of SLT per week) is a key predictor of SLT outcome. The scientific evidence to support the efficacy of SLT is unsatisfactory to date given the lack of randomized controlled trials (RCT), particularly with respect to chronic aphasia (lasting for >6 months after initial stroke). This randomized waiting list-controlled multi-centre trial examines whether intensive integrative language therapy provided in routine in- and outpatient clinical settings is effective in improving everyday communication in chronic post-stroke aphasia.Methods/design: Participants are men and women aged 18 to 70 years, at least 6 months post an ischemic or haemorrhagic stroke resulting in persisting language impairment (i.e., chronic aphasia); 220 patients will be screened for participation, with the goal of including 168 patients during the 26-month recruitment period. Basic language production and comprehension abilities need to be preserved (as assessed by the Aachen Aphasia Test).Therapy consists of language-systematic and communicative-pragmatic exercises for at least 2 hours/day and at least 10 hours/week, plus at least 1 hour self-administered training per day, for at least three weeks. Contents of therapy are adapted to patients' individual impairment profiles.Prior to and immediately following the therapy/waiting period, patients' individual language abilities are assessed via primary and secondary outcome measures. The primary (blinded) outcome measure is the A-scale (informational content, or 'understandability', of the message) of the Amsterdam-Nijmegen Everyday Language Test (ANELT), a standardized measure of functional communication ability. Secondary (unblinded) outcome measures are language-systematic and communicative-pragmatic language screenings and questionnaires assessing life quality as viewed by the patient as well as a relative.The primary analysis tests for differences between the therapy group and an untreated (waiting list) control group with respect to pre- versus post 3-week-therapy (or waiting period, respectively) scores on the ANELT A-scale. Statistical between-group comparisons of primary and secondary outcome measures will be conducted in intention-to-treat analyses.Long-term stability of treatment effects will be assessed six months post intensive SLT (primary and secondary endpoints).Trial registration: Registered in ClinicalTrials.gov with the Identifier NCT01540383.
    Trials 09/2013; 14(1):308. · 2.21 Impact Factor
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    ABSTRACT: The rs17070145 polymorphism (C → T substitution, intron 9) of the KIBRA gene has recently been associated with episodic memory and cognitive flexibility. These findings were inconsistent across reports though, and largely lacked gene-gene or gene-environment interactions. The aim of the present study was to determine the impact of the rs17070145 polymorphism on clinically relevant cognitive domains and its interaction with the modifiers 'lifestyle' and 'cardiovascular risk factors'. Five-hundred forty-five elderly volunteers (mean age 64 years, ±7 years, 56% women) accomplished a comprehensive cognitive testing. Principal component analysis was used to reveal the internal structure of the data, rendering four composite scores: verbal memory, word fluency, executive function/psychomotor speed, and working memory. Lifestyle was assessed with a detailed questionnaire, age-associated risk factors by clinical interview and examination. There was no main effect of the rs17070145 genotype on any cognitive composite scores. However, we found worse performance in executive functions for T-allele carriers in the presence of arterial hypertension (β=-0.365, p=0.0077 and 0.031 after Bonferroni correction). This association was further modified by gender, showing the strongest association in hypertensive females (β=-0.500, p=0.0072 and 0.029 after Bonferroni correction). The effect of KIBRA on cognitive function seems to be complex and modified by gender and arterial hypertension.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 02/2011; 36(6):1296-304. · 8.68 Impact Factor
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    ABSTRACT: G-CSF has been shown in animal models of stroke to promote functional and structural regeneration of the central nervous system. It thus might present a therapy to promote recovery in the chronic stage after stroke. Here, we assessed the safety and tolerability of G-CSF in chronic stroke patients with concomitant vascular disease, and explored efficacy data. 41 patients were studied in a double-blind, randomized approach to either receive 10 days of G-CSF (10 µg/kg body weight/day), or placebo. Main inclusion criteria were an ischemic infarct >4 months prior to inclusion, and white matter hyperintensities on MRI. Primary endpoint was number of adverse events. We also explored changes in hand motor function for activities of daily living, motor and verbal learning, and finger tapping speed, over the course of the study. Adverse events (AEs) were more frequent in the G-CSF group, but were generally graded mild or moderate and from the known side-effect spectrum of G-CSF. Leukocyte count rose after day 2 of G-CSF dosing, reached a maximum on day 8 (mean 42/nl), and returned to baseline 1 week after treatment cessation. No significant effect of treatment was detected for the primary efficacy endpoint, the test of hand motor function. These results demonstrate the feasibility, safety and reasonable tolerability of subcutaneous G-CSF in chronic stroke patients. This study thus provides the basis to explore the efficacy of G-CSF in improving chronic stroke-related deficits. ClinicalTrials.gov NCT00298597.
    PLoS ONE 01/2011; 6(5):e19767. · 3.53 Impact Factor
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    ABSTRACT: The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and -regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral sclerosis (ALS). The current pilot study was performed to determine whether treatment with G-CSF in ALS patients is feasible. Ten patients with definite ALS were entered into a double-blind, placebo-controlled, randomized trial. Patients received either 10 µg/kg BW G-CSF or placebo subcutaneously for the first 10 days and from day 20 to 25 of the study. Clinical outcome was assessed by changes in the ALS functional rating scale (ALSFRS), a comprehensive neuropsychological test battery, and by examining hand activities of daily living over the course of the study (100 days). The total number of adverse events (AE) and treatment-related AEs, discontinuation due to treatment-related AEs, laboratory parameters including leukocyte, erythrocyte, and platelet count, as well as vital signs were examined as safety endpoints. Furthermore, we explored potential effects of G-CSF on structural cerebral abnormalities on the basis of voxel-wise statistics of Diffusion Tensor Imaging (DTI), brain volumetry, and voxel-based morphometry. Treatment was well-tolerated. No significant differences were found between groups in clinical tests and brain volumetry from baseline to day 100. However, DTI analysis revealed significant reductions of fractional anisotropy (FA) encompassing diffuse areas of the brain when patients were compared to controls. On longitudinal analysis, the placebo group showed significant greater and more widespread decline in FA than the ALS patients treated with G-CSF. Subcutaneous G-CSF treatment in ALS patients appears as feasible approach. Although exploratory analysis of clinical data showed no significant effect, DTI measurements suggest that the widespread and progressive microstructural neural damage in ALS can be modulated by G-CSF treatment. These findings may carry significant implications for further clinical trials on ALS using growth factors. ClinicalTrials.gov NCT00298597.
    PLoS ONE 01/2011; 6(3):e17770. · 3.53 Impact Factor
  • Agnes Floel, Leonardo G. Cohen
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    ABSTRACT: In this contribution, we first provide an overview of general principles of reorganisation in the human brain, and point out possible biomarkers of recovery. Subsequently, we expand on possibilities of adjuvant therapy in human rehabilitation using cortical stimulation and pharmacological treatments. Finally, we suggest future directions for research in this field.
    Neurobiology of Disease 01/2010; · 5.62 Impact Factor
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    ABSTRACT: Healthy ageing is accompanied by limitations in performance of activities of daily living and personal independence. Recent reports demonstrated improvements in motor function induced by noninvasive anodal direct current stimulation (tDCS) of the primary motor cortex (M1) in young healthy adults. Here we tested the hypothesis that a single session of anodal tDCS over left M1 could facilitate performance of right upper extremity tasks required for activities of daily living (Jebsen-Taylor hand function test, JTT) in older subjects relative to Sham in a double-blind cross-over study design. We found (a) significant improvement in JTT function with tDCS relative to Sham that outlasted the stimulation period by at least 30 min, (b) that the older the subjects the more prominent this improvement appeared and (c) that consistent with previous results in younger subjects, these effects were not accompanied by any overt undesired side effect. We conclude that anodal tDCS applied over M1 can facilitate performance of skilled hand functions required for activities of daily living in older subjects.
    Neurobiology of aging 03/2009; 31(12):2160-8. · 5.94 Impact Factor
  • NeuroImage 01/2009; 47. · 6.25 Impact Factor
  • NeuroImage 01/2009; 47. · 6.25 Impact Factor
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    ABSTRACT: Noninvasive brain stimulation has developed as a promising tool for cognitive neuroscientists. Transcranial magnetic (TMS) and direct current (tDCS) stimulation allow researchers to purposefully enhance or decrease excitability in focal areas of the brain. The purpose of this article is to review information on the use of TMS and tDCS as research tools to facilitate motor memory formation, motor performance, and motor learning in healthy volunteers. Studies implemented so far have mostly focused on the ability of TMS and tDCS to elicit relatively short-lasting motor improvements and the mechanisms underlying these changes have been only partially investigated. Despite limitations, including the scarcity of data, work that has been already accomplished raises the exciting hypothesis that currently available noninvasive transcranial stimulation techniques could modulate motor learning and memory formation in healthy humans and potentially in patients with neurologic and psychiatric disorders.
    Brain Stimulation 10/2008; 1(4):363-9. · 4.54 Impact Factor
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    ABSTRACT: Cognitive deficits are a common consequence of neurologic disease, in particular, of traumatic brain injury, stroke, and neurodegenerative disorders, and there is evidence that specific cognitive training may be effective in cognitive rehabilitation. Several investigations emphasize the fact that interacting with cortical activity, by means of cortical stimulation, can positively affect the short-term cognitive performance and improve the rehabilitation potential of neurologic patients. In this respect, preliminary evidence suggests that cortical stimulation may play a role in treating aphasia, unilateral neglect, and other cognitive disorders. Several possible mechanisms can account for the effects of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) on cognitive performance. They all reflect the potential of these methods to improve the subject's ability to relearn or to acquire new strategies for carrying out behavioral tasks. The responsible mechanisms remain unclear but they are most likely related to the activation of impeded pathways or inhibition of maladaptive responses. Modifications of the brain activity may assist relearning by facilitating local activity or by suppressing interfering activity from other brain areas. Notwithstanding the promise of these preliminary findings, to date no systematic application of these methods to neurorehabilitation research has been reported. Considering the potential benefit of these interventions, further studies taking into consideration large patient populations, long treatment periods, or the combination of different rehabilitation strategies are needed. Brain stimulation is indeed an exciting opportunity in the field of cognitive neurorehabilitation, which is clearly in need of further research.
    Brain Stimulation 10/2008; 1(4):326-36. · 4.54 Impact Factor
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    ABSTRACT: The endogenous dopamine system is a potent modulator of motor function and learning. Previous studies have demonstrated that, in the elderly, age-related degeneration of the nigrostriatal dopamine system may contribute to deficits in execution of skilled motor functions. The present double-blind, randomized cross-over study examined whether pharmacologically replenishing dopamine improves the execution of complex motor tasks. Twenty healthy young and 20 healthy elderly subjects were studied in two different sessions: (i) after three doses of levodopa (each 100 mg levodopa plus 25 mg carbidopa) and (ii) after three doses of placebo. For each session, subjects completed a functional motor test that reflects hand activities of daily living (Jebsen-Taylor test). In the elderly, but not in the young, Jebsen-Taylor test performance improved significantly (4%) with levodopa compared with placebo, particularly for fine motor functions. Attention to the task, level of fatigue, and positive and negative feelings were similar between sessions. These results demonstrate that increasing the dopaminergic drive pharmacologically may be helpful when the motor system is challenged in the ageing process.
    European Journal of Neuroscience 04/2008; 27(5):1301-7. · 3.75 Impact Factor
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    ABSTRACT: Normal aging is associated with a decrease in dopaminergic function and a reduced ability to form new motor memories with training. This study examined the link between both phenomena. We hypothesized that levodopa would (a) ameliorate aging-dependent deficits in motor memory formation, and (b) increase dopamine availability at the dopamine type 2-like (D2) receptor during training in task-relevant brain structures. The effects of training plus levodopa (100mg, plus 25mg carbidopa) on motor memory formation and striatal dopamine availability were measured with [(11)C]raclopride (RAC) positron emission tomography (PET). We found that levodopa did not alter RAC-binding potential at rest but it enhanced training effects on motor memory formation as well as dopamine release in the dorsal caudate nucleus. Motor memory formation during training correlated with the increase of dopamine release in the caudate nucleus. These results demonstrate that levodopa may ameliorate dopamine deficiencies in the elderly by replenishing dopaminergic presynaptic stores, actively engaged in phasic dopamine release during motor training.
    Neurobiology of aging 03/2008; 29(2):267-79. · 5.94 Impact Factor
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    ABSTRACT: Noninvasive brain stimulation has developed as a promising tool for cognitive neuroscientists. Transcranial magnetic (TMS) and direct current (tDCS) stimulation allow researchers to purposefully enhance or decrease excitability in focal areas of the brain. The purpose of this paper is to review information on the use of TMS and tDCS as research tools to facilitate motor memory formation, motor performance and motor learning in healthy volunteers. Studies implemented so far have mostly focused on the ability of TMS and tDCS to elicit relatively short lasting motor improvements and the mechanisms underlying these changes have been only partially investigated. Despite limitations including the scarcity of data, work that has been already accomplished raises the exciting hypothesis that currently available noninvasive transcranial stimulation techniques could modulate motor learning and memory formation in healthy humans and potentially in patients with neurological and psychiatric disorders.
    Brain Stimul. 01/2008; 1(4):363-369.
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    ABSTRACT: Ischemia-induced cutaneous anesthesia of the healthy hand in patients with chronic stroke elicits transient improvements of motor performance in the contralateral, paretic hand. The present study was designed to investigate one of the possible mechanisms underlying this effect. The authors evaluated the effects of transient ischemic cutaneous anesthesia of the healthy hand (target intervention) and healthy foot (control intervention) on transcranial magnetic stimulation-induced interhemispheric inhibition from the contralesional onto the ipsilesional primary motor cortex (M1). Ten subjects with chronic, predominantly subcortical stroke with motor impairment were assessed. Cutaneous anesthesia of the intact hand but not the intact leg resulted in reduction of the inhibitory drive from the contralesional to the ipsilesional M1 both at rest and immediately preceding movements of the paretic hand. Changes in premovement interhemispheric inhibition showed a trend for correlation with improvements in finger-tapping speed in the paretic hand. The findings suggest that modulation of interhemispheric inhibitory interactions between the contralesional and ipsilesional M1, either primarily or secondary to intrahemispheric excitability changes in either hemisphere, may contribute to performance improvements with cutaneous anesthesia of the intact hand. The present study provides additional insight into the mechanisms by which rehabilitative interventions focused on training one hand and restraining the other may operate after chronic stroke.
    Neurorehabilitation and neural repair 01/2008; 22(5):477-85. · 4.28 Impact Factor
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    ABSTRACT: Noninvasive brain stimulation has developed as a promising tool for cognitive neuroscientists. Transcranial magnetic (TMS) and direct current (tDCS) stimulation allow researchers to purposefully enhance or decrease excitability in focal areas of the brain. The purpose of this paper is to review information on the use of TMS and tDCS as research tools to facilitate motor memory formation, motor performance and motor learning in healthy volunteers. Studies implemented so far have mostly focused on the ability of TMS and tDCS to elicit relatively short lasting motor improvements and the mechanisms underlying these changes have been only partially investigated. Despite limitations including the scarcity of data, work that has been already accomplished raises the exciting hypothesis that currently available noninvasive transcranial stimulation techniques could modulate motor learning and memory formation in healthy humans and potentially in patients with neurological and psychiatric disorders.
    Brain Stimul. 01/2008; 1(4):363-369.
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    ABSTRACT: Regular physical exercise improves cognitive functions and lowers the risk for age-related cognitive decline. Since little is known about the nature and the timing of the underlying mechanisms, we probed whether exercise also has immediate beneficial effects on cognition. Learning performance was assessed directly after high impact anaerobic sprints, low impact aerobic running, or a period of rest in 27 healthy subjects in a randomized cross-over design. Dependent variables comprised learning speed as well as immediate (1 week) and long-term (>8 months) overall success in acquiring a novel vocabulary. Peripheral levels of brain-derived neurotrophic factor (BDNF) and catecholamines (dopamine, epinephrine, norepinephrine) were assessed prior to and after the interventions as well as after learning. We found that vocabulary learning was 20 percent faster after intense physical exercise as compared to the other two conditions. This condition also elicited the strongest increases in BDNF and catecholamine levels. More sustained BDNF levels during learning after intense exercise were related to better short-term learning success, whereas absolute dopamine and epinephrine levels were related to better intermediate (dopamine) and long-term (epinephrine) retentions of the novel vocabulary. Thus, BDNF and two of the catecholamines seem to be mediators by which physical exercise improves learning.
    Neurobiology of Learning and Memory 05/2007; 87(4):597-609. · 3.33 Impact Factor
  • A Floel, L G Cohen
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    ABSTRACT: In the memory domain, a large body of experimental evidence about subsystems of memory has been collected from classic lesion studies and functional brain imaging. Animal studies have provided information on molecular mechanisms of memory formation. Compared to this work, transcranial magnetic stimulation and transcranial direct current stimulation have made their own unique contribution. Here, we describe how noninvasive brain stimulation has been used to study the functional contribution of specific cortical areas during a given memory task, how these techniques can be used to assess LTP- and LTD-like plasticity in the living human brain, and how they can be employed to modulate memory formation in humans, suggesting an adjuvant role in neurorehabilitative treatments following brain injury.
    Brain Research Reviews 03/2007; 53(2):250-9. · 7.82 Impact Factor
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    Agnes Floel, Leonardo G Cohen
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    ABSTRACT: Stroke is the leading cause of adult disability in the western world. Consensus has built over the last few years regarding the usefulness of training to improve motor disability resulting from stroke. Until recently, there were no accepted strategies to enhance the beneficial effects of training. However, the combination of basic and clinical science data over the last few years is changing this picture, and is highly relevant to the field of neurorehabilitation. Human studies in both healthy individuals and patients after brain damage demonstrate as a proof of principle that somatosensory input, cortical stimulation, interhemispheric interactions, and pharmacologic interventions can modulate cortical plasticity in neurorehabilitation after stroke. These findings strongly suggest directions in the development of novel strategies to enhance training effects on motor recovery. The intent of this review is to describe these strategies, the basic science principles on which they are based, and the clinical applications that have emerged so far.
    Cognitive and Behavioral Neurology 04/2006; 19(1):1-10. · 1.19 Impact Factor
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    ABSTRACT: Previous studies showed that anodal transcranial DC stimulation (tDCS) applied to the primary motor cortex of the affected hemisphere (M1affected hemisphere) after subcortical stroke transiently improves performance of complex tasks that mimic activities of daily living (ADL). It is not known if relatively simpler motor tasks are similarly affected. Here we tested the effects of tDCS on pinch force (PF) and simple reaction time (RT) tasks in patients with chronic stroke in a double-blind cross-over Sham-controlled experimental design. Anodal tDCS shortened reaction times and improved pinch force in the paretic hand relative to Sham stimulation, an effect present in patients with higher impairment. tDCS of M1affected hemisphere can modulate performance of motor tasks simpler than those previously studied, a finding that could potentially benefit patients with relatively higher impairment levels.
    BMC Neuroscience 02/2006; 7:73. · 3.00 Impact Factor
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    ABSTRACT: The effects of a single oral dose of levodopa administered in a randomized, double-blind, placebo-controlled cross-over design on formation of a motor memory were studied by a training protocol in patients with chronic stroke. Levodopa enhanced the ability of motor training to encode an elementary motor memory relative to placebo. Up-regulation of dopaminergic function may enhance motor memory formation, crucial for successful rehabilitative treatments in patients with chronic stroke.
    Neurology 09/2005; 65(3):472-4. · 8.30 Impact Factor

Publication Stats

1k Citations
188.54 Total Impact Points

Institutions

  • 2011
    • Charité Universitätsmedizin Berlin
      • Department of Nephrology
      Berlin, Land Berlin, Germany
  • 2009–2011
    • Universitätsklinikum Münster
      Muenster, North Rhine-Westphalia, Germany
    • University of Hamburg
      • Department of Neurology
      Hamburg, Hamburg, Germany
  • 2007–2010
    • University of Münster
      • Department of Neurology
      Münster, North Rhine-Westphalia, Germany
  • 2003–2008
    • National Institutes of Health
      Maryland, United States
  • 2004
    • Hebrew University of Jerusalem
      • Department of Neurobiology
      Jerusalem, Jerusalem District, Israel