R Benecke

University of Rostock, Rostock, Mecklenburg-Vorpommern, Germany

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Publications (317)1089.77 Total impact

  • Movement Disorders 11/2014; · 5.63 Impact Factor
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    ABSTRACT: Glucocorticosteroids (GCS) are widely used for the treatment of neurological diseases, e.g. multiple sclerosis. High levels of GCS are toxic to the central nervous system and can produce adverse effects. The effect of methylprednisolone (MP) on mammalian neuronal networks was studied in vitro. We demonstrate a dose-dependent excitatory effect of MP on cultured neuronal networks, followed by a shut-down of electrical activity using the microelectrode array technique.
    Cellular and Molecular Neurobiology 10/2014; · 2.20 Impact Factor
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    ABSTRACT: Objectives:Multiple sclerosis (MS) is an autoimmune disease affecting young people and is a major cause of disability. In the course of time, disability progresses and symptoms like spasticity may occur. Spasticity is a major cost factor in MS patients. Various agents are approved for the treatment of spasticity, but each of those agents may have several side effects. Intrathecally administered steroids (triamcinolone-acetonide (TCA)) may be efficient in treating spasticity in patients with lesions in the spinal cord and no response to first-line therapeutics. The aim of this study is to show effects of TCA treatment on clinical parameters in patients with MS.Methods:This multicentre open label study included 54 patients with MS. The clinical outcome parameters were spasticity, disability, maximum walking distance, bladder function and quality of life. All patients received physiotherapy in addition to TCA treatment to obtain optimal effects on clinical parameters.Results:Spasticity, maximum walking distance as well as disability improved significantly (P⩽0.001) during TCA applications. Bladder function improved in every seventh patient.Conclusion:We observed the effects of intrathecally administered TCA on different clinical parameters including bladder function. TCA administration is a safe method to treat different symptoms in MS patients. Longitudinal trials with repeated TCA cycles are needed to show long-term effects. Besides TCA treatment, physiotherapy contributes to the improvement of clinical parameters.Spinal Cord advance online publication, 16 September 2014; doi:10.1038/sc.2014.155.
    Spinal Cord 09/2014; · 1.70 Impact Factor
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    ABSTRACT: Major depressive disorder (MDD) has been associated with an increased risk of subsequent Parkinson's disease (PD) in case-control and cohort studies. However, depression alone is unlikely to be a useful marker of prodromal PD due to its low specificity. In this longitudinal observational study, we assessed whether the presence of other potential markers of prodromal PD predicts the subsequent development of PD in MDD patients. Of 57 patients with severe MDD but no diagnosis of PD who underwent a structured interview, olfactory and motor investigation and transcranial sonography at baseline, 46 (36 women; mean age 54.9 ± 11.7 years) could be followed for up to 11 (median, 10) years. Three patients (2 women; age 64, 65 and 70 years) developed definite PD after 1, 7, and 9 years, respectively. The combined finding of mild asymmetric motor slowing, idiopathic hyposmia, and substantia nigra hyperechogenicity predicted subsequent PD in all patients who could be followed for longer than 1 year. Out of the whole study cohort, only the subjects with subsequent PD presented with the triad of asymmetric motor slowing, idiopathic hyposmia, and substantia nigra hyperechogenicity in combination with at least two out of four reportable risk factors (family history of PD, current non-smoker, non-coffee drinker, constipation) at baseline investigation. Post-hoc analysis revealed that additional rating of eye and eye-lid motor abnormalities might further improve the prediction of PD in larger cohorts. Findings of this pilot-study suggest that MDD patients at risk of subsequent PD can be identified using an inexpensive non-invasive diagnostic battery.
    Journal of Neural Transmission 09/2014; · 2.87 Impact Factor
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    ABSTRACT: •PML is rare and normally manifests in persons with a compromised immune system.•We describe an apparently immunocompetent old patient who developed PML.•We identified a pre-clinical PBC as exclusive risk factor for PML manifestation•We present this first description of a PML in association with a possible or early stage PBC.
    Clinical Neurology and Neurosurgery 08/2014; · 1.25 Impact Factor
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    ABSTRACT: To determine longitudinal rates of cortical atrophy in classical Amyotrophic lateral sclerosis (ALS) and ALS variants. Rates of cortical thinning were determined between 2 scans, 3-15 months apart, in 77 ALS patients: 51 classical, 12 upper motor neuron (UMN), and 14 lower motor neuron (LMN) ALS variants. Cortical thickness at the first assessment was compared with 60 healthy controls matched by age and gender. Atrophy rates were compared between patient sub-groups and correlated with disease duration, progression, and severity. Using a cross-sectional analysis, we found a significant difference in cortical thickness between ALS patients and controls in the motor and extra-motor areas (left medial orbito frontal gyrus, left inferior parietal gyrus, bilateral insular cortex, right fusiform gyrus, bilateral precuneus). Using a longitudinal analysis, we found a significant decline of cortical thickness in frontal, temporal, and parietal regions over the course of the study in ALS patients. Effects were independent of the clinical subtype, with exception of the precentral gyrus (p < 0.001). The LMN ALS variants demonstrated the highest rates of cortical thinning in the precentral gyrus, the UMN-dominant subjects exhibited intermediate rates of atrophy, and the classical ALS patients exhibited no such change. Atrophy of the precentral gyrus in classical ALS indicates a floor effect at the first assessment, resulting in a lack of further atrophy over time. Structural loss of the precentral gyrus appears to be an early sign of classical ALS. Over time, patterns of cortical thinning in extra-motor areas can be identified in ALS, regardless of the phenotype.
    Journal of Neurology 07/2014; · 3.84 Impact Factor
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    ABSTRACT: Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adults. Over time, the disease progresses and, with accumulating disability, symptoms such as spasticity may occur. Although several treatment options are available, some patients may not respond to first-line therapeutics. However, some of these patients may benefit from intrathecally administered triamcinolone-acetonide (TCA), a derivative of glucocorticosteroids (GCS). GCS may have neurotoxic effects, and cell apoptosis may occur. The aim of this study was to investigate the effects of TCA on biomarkers in the cerebrospinal fluid (CSF) suggestive of neurodegeneration.
    Molecular Diagnosis & Therapy 07/2014; · 2.59 Impact Factor
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    ABSTRACT: Hypercalcemia can cause a subacute syndrome of progressive dementia and marked changes in the electroencephalogram (EEG). We report a case of iatrogenic hypercalcemia with a close correlation between the clinical course and the EEG changes. A 73-year-old woman presented with a subacute syndrome of progressive dementia and bursts of 1.5 to 2 Hz intermittent rhythmic delta activity superimposed on a low-voltage background activity in the EEG. Clinical and EEG abnormalities rapidly resolved after normalization of serum calcium levels. As part of the diagnostic workup of a subacute progressive dementia, a serum calcium level and an EEG should be obtained to detect a Creutzfeldt-Jakob like syndrome in hypercalcemia. Unlike in Creutzfeldt-Jakob disease, and Creutzfeldt-Jakob-like syndrome induced by lithium intoxication, there are rarely myoclonic jerks and periodic discharges in hypercalcemic encephalopathy.
    Clinical EEG and neuroscience: official journal of the EEG and Clinical Neuroscience Society (ENCS) 06/2014; · 3.16 Impact Factor
  • Acta neurologica Belgica. 04/2014;
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    ABSTRACT: Clinically Isolated Syndromes (CIS) summarize clinical features of possible multiple sclerosis (MS) as a first clinical event of the disease. Escalation therapy in CIS episodes comprises high dose glucocorticosteroid (GCS) treatment followed by therapeutic plasma exchange (TPE) in patients unresponsive to GCS. The aim of our study was to analyze TPE effects in CIS patients. Eleven GCS-unresponsive patients exhibiting CIS were treated with TPE. A median of 5.0 (range 3-8) treatments were performed with a median exchange volume of 3.0 L (range 2.2-3.5 L). Standard diagnostic results in CIS patients were collected. In 10 out of 11 patients clinical improvement was observed. In Expanded Disability Status Scale (EDSS) Scoring, a commonly used score to assess disability in MS and CIS patients, significant improvement was shown as well. One patient was a non-responder to TPE. Apheresis treatments were well tolerated in all patients. In the medical control of GCS-unresponsive CIS episodes, TPE appears to be an effective and well-tolerated treatment option. TPE response in CIS patients is comparable to TPE results in GCS-unresponsive MS relapses. Further prospective studies are indicated.
    Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 03/2014; · 1.53 Impact Factor
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    ABSTRACT: Tremulous Parkinson's disease (PD) and essential tremor are well known to be associated, but characteristics of progression of pure tremor state to PD remain unclear. In this prospective study a cohort of 16 patients suffering from a suggested new disease entity was clinically, pharmacologically, and sonographically analyzed to evaluate whether characteristics giving rise to a new entity in this field can be detected. All patients had a history of asymmetric postural tremor (aPT) who either already had developed surplus Parkinsonism (PARK group), or were still in the state of a pure asymmetric postural tremor syndrome (APT group). Asymmetry of aPT was assessed by tremor scores including an asymmetry index. DOPA-responsivity was analyzed by tremor scores and the score of the motor part of the Unified Parkinson's disease rating scale. Transcranial brain sonography was performed to evaluate echogenicity of the substantia nigra. Mean age at onset of asymmetric postural tremor was 57 ± 8.5 years without significant differences between both groups. Family history was compatible with an autosomal- dominant inheritance pattern in the majority of patients of both the aPT and PARK group. All patients in the PARK group and 3 out of 8 patients in the APT group (38%) with respect to their asymmetric postural tremor were DOPA-responsive. All patients of both groups eligible to transcranial brain sonography showed hyperechogenicity of substantia nigra. In both groups, there was no correlation between tremor severity and duration of asymmetric postural tremor. Our data indicate that patients with an initial asymmetric and sometimes DOPA-responsive postural tremor syndrome and PARK patients are at various stages within the transition from aPT to a later developed DOPA-responsive Parkinsonian syndrome. It is postulated that the described group of patients may represent a separate disease entity with a hereditary background.
    Journal of Parkinson's disease. 01/2014;
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    ABSTRACT: A relevant fraction of patients with amyotrophic lateral sclerosis (ALS) exhibit a fronto-temporal pattern of cognitive and behavioural disturbances with pronounced deficits in executive functioning and cognitive control of behaviour. Structural imaging shows a decline in fronto-temporal brain areas, but most brain imaging studies did not evaluate cognitive status. We investigated microstructural white matter changes underlying cognitive impairment using diffusion tensor imaging (DTI) in a large cohort of ALS patients. We assessed 72 non-demented ALS patients and 65 matched healthy control subjects using a comprehensive neuropsychological test battery and DTI. We compared DTI measures of fiber tract integrity using tract-based spatial statistics among ALS patients with and without cognitive impairment and healthy controls. Neuropsychological performance and behavioural measures were correlated with DTI measures. Patients without cognitive impairment demonstrated white matter changes predominantly in motor tracts, including the corticospinal tract and the body of corpus callosum. Those with impairments (ca. 30%) additionally presented significant white matter alterations in extra-motor regions, particularly the frontal lobe. Executive and memory performance and behavioural measures were correlated with fiber tract integrity in large association tracts. In non-demented cognitively impaired ALS patients, white matter changes measured by DTI are related to disturbances of executive and memory functions, including prefrontal and temporal regions. In a group comparison, DTI is able to observe differences between cognitively unimpaired and impaired ALS patients.
    PLoS ONE 01/2014; 9(12):e114543. · 3.53 Impact Factor
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    ABSTRACT: This prospective study was performed to investigate whether verbal memory deficits are present in patients with a first unprovoked seizure irrespective of significant lesions in the brain and whether symptoms of depression were experienced by those patients in the week before the seizure. After having given informed consent, patients who presented with a first unprovoked seizure were investigated with a psychometric battery consisting of a verbal memory test, a figural memory test, a test following the Stroop paradigm, and a self-rating scale for depression in addition to the routine diagnostic work-up with EEG and MRI. The data of 53 patients aged 45years on average (33 males and 20 females) were available. Verbal memory deficits were present in 60% of the patients, and 21% of the patients delivered a self-rating that was suggestive of at least minor depression in the week before the seizure. Neither verbal memory deficits nor symptoms of depression were associated with a significant lesion of the brain. There was a significant negative correlation between immediate recall in the verbal memory test and the score in the self-rating scale for depression. Our data suggest that even at the time of the first unprovoked seizure, there is an epileptic condition of the brain, which facilitates the occurrence of verbal memory deficits and depression in the presence of an epileptogenic focus irrespective of its localization.
    Epilepsy & Behavior 11/2013; · 2.06 Impact Factor
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    ABSTRACT: Spinal and bulbar muscular atrophy (SBMA), Kennedy's disease, is an adult-onset hereditary neurodegenerative disorder, associated predominantly with a lower motor neuron syndrome and eventually endocrine and sensory disturbances. In contrast to other motor neuron diseases such as amyotrophic lateral sclerosis (ALS), the impairment of cognition in SBMA is not well documented. We conducted a systematic cross-sectional neuropsychological study in order to investigate cognition in SBMA patients more thoroughly. We investigated 20 genetically proven SBMA patients compared to 20 age- and education-matched control subjects using a comprehensive neuropsychological test battery, measuring executive functioning, attention, memory and visuospatial abilities. The SBMA patients performed significantly worse than healthy controls in three sub-tests in the executive and attention domains. This low performance was in the working memory (digit span backward task), verbal fluency category (single letter fluency task) and memory storage capacity (digit span forward task). No disturbances were detected in other cognitive domains. The impairments were subclinical and not relevant to the patients' everyday functioning. In addition, no correlations were found between cognitive scores and the CAG repeat length. In conclusion, we found minor cognitive disturbances in patients with SBMA, which could indicate subtle frontal lobe dysfunction. These findings extend our neurobiological understanding of SBMA.
    Amyotrophic lateral sclerosis & frontotemporal degeneration. 11/2013;
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    ABSTRACT: The detection of Parkinson's disease (PD) at stages earlier than current diagnostic criteria allow for may increase the efficacy of disease-modifying therapies. Here we studied the relationship between retrospectively reported prodromal non-motor and motor features of PD, their pre-diagnostic presentation to physicians, and the extrapolated potential of an earlier diagnosis of PD considering early diagnostic markers detected at presence. One hundred and fifteen PD patients (41 women; age 63.2 ± 8.6 years) underwent a structured face-to-face interview on 22 prediagnostic symptoms. Present olfactory function, motor symptoms, and substantia nigra hyperechogenicity (SN-h) were assessed using standardized tools. Most frequently self-perceived symptoms in the early and very early prediagnostic phase (>2, >7 years prior to diagnosis) were hyposmia (23, 10 %), musculoskeletal pain (21, 9 %), and depression/anxiety (14, 11 %). In the late prediagnostic phase (≤2 years) mild motor signs, especially asymmetric bradykinesia and rest tremor, increasingly dominated the self-perception. In the prediagnostic phase, 99 % of patients consulted a physician because of motor symptoms but only 36 % with non-motor symptoms, mostly pain (20 %), depression/anxiety (9 %), constipation, bladder urgency, insomnia, REM sleep behaviour disorder, sexual dysfunction, and malignant melanoma (each, <6 %). Assuming the potential detectability of present hyposmia, asymmetric motor slowing and SN-h, a triad highly specific for PD, as early as 5 years prior to diagnosis, up to 84 (73 %) patients could have been identified in the prediagnostic phase using their or their physicians' awareness of early symptoms. We conclude that educating the general population and physicians on the importance of distinct prodromal features and applying symptom-specific diagnostic programs can improve the early detection of PD.
    Journal of Neurology 10/2013; · 3.84 Impact Factor
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    ABSTRACT: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently defined inflammatory central nervous system (CNS) disorder, prominently involving the brainstem and in particular the pons. The condition features a combination of clinical symptoms essentially referable to brainstem pathology and a characteristic MRI appearance with punctate and curvilinear gadolinium enhancement "peppering" the pons. The radiological distribution is focused in the pons and adjacent rhombencephalic structures such as the cerebellar peduncles, cerebellum, medulla, and the midbrain. While the lesion burden with a perivascular pattern is typically most dense in these pontine and peripontine regions, enhancing lesions may additionally extend into the spinal cord and supratentorial structures such as the thalamus, basal ganglia, capsula interna, corpus callosum, and the cerebral white matter. Another core feature is clinical and radiological responsiveness to glucocorticosteroid (GCS) based immunosuppression. As withdrawal of GCS treatment results commonly into disease exacerbation, a long-term immunosuppressive therapy appears to be mandatory for sustained improvement. Diagnosis of CLIPPERS is challenging and requires careful exclusion of alternative diagnoses. A specific serum or CSF biomarker for the disorder is currently not known. Pathogenesis of CLIPPERS remains poorly understood and the nosological position of CLIPPERS has still to be established. Whether CLIPPERS represents an independent, actual new disorder or a syndrome that includes etiologically heterogeneous diseases and/or their prestages, remains a debated and not finally clarified issue. Clinicians and radiologists should be aware of this condition and its differential diagnoses, given that CLIPPERS constitutes a treatable condition and that patients may benefit from an early introduction of GCS ensued by a long-term immunosuppression. Based on previous reports in literature - currently encompassing more than 50 reported cases of CLIPPERS - this review addresses clinical features, diagnostic criterias, differential diagnoses and therapeutic management of this peculiar disorder.
    Clinical & Experimental Immunology 09/2013; · 3.28 Impact Factor
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    ABSTRACT: Amyotrophic lateral sclerosis (ALS) is characterised by degeneration of upper (UMN) and lower motor neurons (LMN).We aimed to relate clinical variables to cortical thinning of the primary motor cortex (PMC). The PMC was defined as the region of interest in high-resolution structural MRI scans. We related vertex-wise measures of cortical thinning to UMN involvement, bulbar/limb onset, the total ALS functional rating scale (ALSFRS-R), and its bulbar and upper limb subscore. In total, 93 ALS patients were recruited (60 with classical ALS; 17 with dominant UMN, e.g., primary lateral sclerosis; 16 with pure LMN variant, e.g., progressive muscular atrophy, flail arm or leg syndrome) and compared to 67 age and gender matched healthy controls. The UMN signs in the bulbar regions were associated with bilateral thinning within the bulbar segment on the motor cortex, and UMN signs in spinal regions were associated with thinning in the limb segment of the motor cortex. The site of disease onset (bulbar/lower limb) exhibited the most pronounced thinning in the corresponding part of the motor cortex. According to our analysis, dominant UMN patients demonstrated the most distinct thinning followed by classical ALS patients. Pure LMN variants did not differ from healthy controls. The bulbar subscore of the ALSFRS-R correlated with thinning of the left inferior PMC. Focal morphological changes within the PMC correspond to clinically measured impairments and depend on disease phenotype. Measuring cortical thickness may potentially offer an objective in vivo marker to quantify disease pathology.
    Journal of Neurology 08/2013; · 3.84 Impact Factor
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    ABSTRACT: Clinical, genetic, and pathological findings suggest a close relationship between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We studied the patterns of cortical atrophy across the spectrum between ALS and ALS-FTD. A surface-based morphometry analysis based on an age- and sex-matched sample of 81 ALS patients and 62 healthy control subjects (HC) was conducted. In addition, we used an age-matched subsample of 57 ALS patients and 31 HC to compare cortical thickness between 3 groups of neuropsychologically characterized ALS patients: (1) cognitively unimpaired; (2) cognitively impaired; and (3) ALS-FTD patients. Compared with HC, the entire sample of patients demonstrated cortical thinning in the bilateral precentral gyrus, right precuneus, and right frontal and temporal lobes. ALS-FTD patients showed cortical thinning in regions including the frontal and temporal gyri and the posterior cingulate cortex. Cognitively impaired ALS patients showed cortical thinning in regions largely overlapping with those found in ALS-FTD, but changes were less widespread. In conclusion, the cognitive status of ALS subjects is associated with different patterns of cortical atrophy.
    Neurobiology of aging 08/2013; · 5.94 Impact Factor
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    ABSTRACT: Since randomized controlled trials are difficult to perform for ethical reasons in a potentially deadly condition like status epilepticus (SE), a retrospective database analysis may be welcome to broaden the evidence for the treatment of SE. In this retrospective study we evaluated every SE treatment at the neurological department of the University of Rostock from January 2000 to December 2009 in order to determine the efficacy of different antiepileptic drugs (AEDs) in terminating different kinds of SE. We analyzed the frequency of refractory courses in different types of SE, at which time which AED was administered and at which time which AED was effective to terminate the different epileptic conditions. A second aim of this study was to evaluate the course and the outcome of different kinds of SE. Statistical comparisons were performed with the χ(2)-test. 167 episodes of SE in 118 patients could be evaluated. The efficacy rates of AEDs differed significantly, mainly due to the superior efficacy of clonazepam (CZP). CZP seemed to be more effective than DZP, LEV, MDM and VPA in terminating generalized convulsive status epilepticus (GCSE), whereas there was no significant difference in the efficacy for terminating nonconvulsive status epilepticus (NCSE) and epilepsia partialis continua (EPC) between the used AEDs. Anaesthesia and CZP both terminated GCSE more effectively than NCSE and EPC. Concerning the course of the different kinds of SE the following results were obtained: 13 patients died during hospital treatment. Treatment in NCSE and EPC started significantly later than in GCSE. There was no significant difference in mortality between the types of SE. However the frequency of refractory courses differed between the types of SE. At the time of SE termination without the administration of anaesthesia a combination therapy using 2 or more AEDs was established in most episodes.
    Epilepsy research 08/2013; · 2.48 Impact Factor
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    ABSTRACT: The breach rhythm is sometimes considered the consequence of reduced resistance between the cortex and the scalp electrode in the region of a skull defect. On the other hand, the electroencephalographic (EEG) changes after craniotomy were attributed to an activation of EEG activity by meningocortical adhesions with admixed gliosis. We report changes of the breach rhythm in a patient with astrocytoma, which give further evidence that the breach rhythm is not merely the result of physical changes in the area of a skull defect. In our patient, the breach rhythm was no longer detectable before a new tumor progression took place, showed up again, and at the end changed into localized slowing before the deterioration of the patient's general medical condition. This case suggests that in patients with brain tumors, the loss or attenuation in frequency of an established breach rhythm might be considered as an indication of a new tumor progression.
    Clinical EEG and neuroscience: official journal of the EEG and Clinical Neuroscience Society (ENCS) 07/2013; 44(3):237-243. · 3.16 Impact Factor

Publication Stats

9k Citations
1,089.77 Total Impact Points


  • 1997–2014
    • University of Rostock
      • • Klinik und Poliklinik für Neurologie
      • • Zentrum für Nervenheilkunde
      Rostock, Mecklenburg-Vorpommern, Germany
  • 2013
    • Deutsches Zentrum für Neurodegenerative Erkrankungen
      Bonn, North Rhine-Westphalia, Germany
  • 2012
    • University of Wuerzburg
      • Department of Neurology
      Würzburg, Bavaria, Germany
  • 2009
    • University of Cologne
      • Department of Neurology
      Köln, North Rhine-Westphalia, Germany
  • 2002
    • Goethe-Universität Frankfurt am Main
      Frankfurt, Hesse, Germany
    • Christian-Albrechts-Universität zu Kiel
      • Unit of Neurobiology
      Kiel, Schleswig-Holstein, Germany
  • 1988–1999
    • Heinrich-Heine-Universität Düsseldorf
      • Neurologische Klinik
      Düsseldorf, North Rhine-Westphalia, Germany
  • 1998
    • University of Freiburg
      Freiburg, Baden-Württemberg, Germany
  • 1996–1997
    • Universitätsklinikum Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany
  • 1992
    • Deutsches Herzzentrum München
      München, Bavaria, Germany
  • 1991
    • Technische Universität München
      • Neurologische Klinik und Poliklinik
      München, Bavaria, Germany
  • 1988–1990
    • Universitätsmedizin Göttingen
      • Department of Clinical Neurophysiology
      Göttingen, Lower Saxony, Germany
  • 1986–1988
    • University of London
      • The School of Pharmacy
      Londinium, England, United Kingdom
  • 1980–1988
    • Georg-August-Universität Göttingen
      Göttingen, Lower Saxony, Germany