R Benecke

Deutsches Zentrum für Neurodegenerative Erkrankungen, Bonn, North Rhine-Westphalia, Germany

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Publications (295)962.54 Total impact

  • 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: 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; · 1.84 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; · 3.58 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; · 3.41 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; · 3.58 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. · 1.82 Impact Factor
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    ABSTRACT: Homozygous or compound heterozygous mutations in the glucocerebrosidase gene cause Gaucher disease. Moreover, heterozygous glucocerebrosidase gene mutations represent the most common genetic risk factor for Parkinson's disease (PD) known so far. Substantia nigra (SN) hyperechogenicity, a sonographic feature thought to reflect iron accumulation, has been described in both PD and Gaucher disease patients. Here we studied how clinical, genetic, and brain sonographic findings relate to the occurrence of PD in Gaucher disease. Sixteen Gaucher disease patients, 12 PD patients, and 32 control subjects were enrolled. The glucocerebrosidase genotypes were identified by DNA sequencing. All subjects underwent transcranial ultrasound, and eight Gaucher disease patients additionally MRI for comparison with SN ultrasound findings. SN hyperechogenicity and reduced echogenicity of brainstem raphe were more frequent in Gaucher disease patients (62, 37 %) than in controls (12, 12 %; p < 0.001, p < 0.05). SN hyperechogenicity in Gaucher disease patients was unrelated to type or severity of glucocerebrosidase gene mutation, but correlated with iron-sensitive MRI-T2 hypointensity of SN pars compacta, and with age at start of enzyme replacement therapy. While none of the five Gaucher disease patients with signs of PD (definite PD, n = 4; early PD, n = 1) had severe glucocerebrosidase gene mutations known to cause neuronopathic Gaucher disease, all carried a N370S allele, previously reported to predict non-neuronopathic Gaucher disease. Hyposmia, higher non-motor symptoms score (constipation, depression, executive dysfunction), and SN hyperechogenicity were characteristic features of Gaucher disease-related PD. We conclude that the combined clinical, genetic, and transcranial sonographic assessment may improve the PD risk evaluation in Gaucher disease.
    Journal of Neurology 06/2013; · 3.58 Impact Factor
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    Acta neurologica Belgica. 06/2013;
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    ABSTRACT: BACKGROUND AND PURPOSE: Abnormalities of the lenticular nucleus (LN) on transcranial sonography (TCS) are a characteristic finding in idiopathic segmental and generalized dystonia. Our intention was to study whether TCS detects basal ganglia abnormalities also in spasmodic dysphonia, an extremely focal form of dystonia. METHODS: Transcranial sonography of basal ganglia, substantia nigra and ventricles was performed in 14 patients with spasmodic dysphonia (10 women, four men; disease duration 16.5 ± 6.1 years) and 14 age- and sex-matched healthy controls in an investigator-blinded setting. RESULTS: Lenticular nucleus hyperechogenicity was found in 12 spasmodic dysphonia patients but only in one healthy individual (Fisher's exact test, P < 0.001) whilst other TCS findings did not differ. The area of LN hyperechogenic lesions quantified on digitized image analysis correlated with spasmodic dysphonia severity (Spearman test, r = 0.82, P < 0.001). CONCLUSION: Our findings link the underlying pathology of spasmodic dysphonia to that of more widespread forms of dystonia.
    European Journal of Neurology 04/2013; · 4.16 Impact Factor
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    ABSTRACT: Botulinum neurotoxin (BoNT) inhibits the release of acetylcholine from presynaptic vesicles through its proteinase activity cleaving the SNARE complex. Parkinson's disease (PD) is associated with locally increased cholinergic activity in the striatum. Therefore, the present study investigates the effect of unilateral intrastriatal BoNT-A injection in naïve rats on striatal morphology; i.e., the total number of Nissl-stained neurons and the volume of caudate-putamen (CPu) were estimated. Furthermore, stainings for markers of gliosis (glial fibrillary acidic protein) and microglia (Iba1) were performed. In addition, the potential beneficial effects of a unilateral intrastriatal injection of BoNT-A on motor activity in the rat model of hemi-PD were evaluated. Hemi-PD was induced by unilateral injection of 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle. Six weeks later, rats received an ipsilateral intrastriatal injection of BoNT-A. Behaviorally, motor performance was tested. The total number of CPu neurons and the striatal volume were not significantly different between the BoNT-A-injected right and the intact left hemispheres of naïve rats. In hemi-PD rats, intrastriatal BoNT-A abolished apomorphine-induced rotations, increased amphetamine-induced rotations, and tended to improve left forelimb usage. Forced motor function in the accelerod test was not significantly changed by BoNT-A, and open field activity was also unaltered compared with sham treatment. Thus, intrastriatal BoNT-A affects spontaneous motor activity of hemi-PD rats to a minor degree compared with drug-induced motor function. In the future, tests assessing the cognitive and emotional performance should be performed to ascertain finally the potential therapeutic usefulness of intrastriatal BoNT-A for PD. © 2013 Wiley Periodicals, Inc.
    Journal of Neuroscience Research 03/2013; · 2.97 Impact Factor
  • Clinical neurology and neurosurgery 02/2013; · 1.30 Impact Factor
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    ABSTRACT: In this study, we sought to determine the patients' attitudes towards generic substitution of antiepileptic drugs (AEDs) and their experiences with the usage of generic antiepileptic drugs in Germany and other German-speaking countries. A questionnaire was designed for a cross-sectional study. Two thousand copies of the questionnaire were delivered with a magazine edited by a patients' organization. Additionally, the questionnaire was placed on the internet platform of another patients' organization. Thirty-two percent of the patients who already experienced a switch to generic AEDs complained of problems with the switch. Patients who answered the magazine survey worried significantly more about generic substitution of AEDs than patients who answered the internet version. Patients who had never switched were more concerned about generic substitution than those who had already switched. Moreover, patients' beliefs differed between the use of generic drugs in acute medical conditions such as pain and infections and the use of generic AEDs in epilepsy.
    Epilepsy & Behavior 02/2013; 27(1):135-139. · 1.84 Impact Factor
  • Eur J Neurol. 01/2013;
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    ABSTRACT: It remains to be determined whether the benefits of botulinum toxin type A (BoNT-A) on cervical dystonia (CD) motor symptoms extend to improvements in patient's quality of life (QoL). This analysis of a large, multicentre study was conducted with the aim of investigating changes in QoL and functioning among de novo patients receiving 500 U BoNT-A (abobotulinumtoxinA; Dysport) for the treatment of the two most frequent forms of CD, predominantly torticollis and laterocollis. A prospective, open-label study of Dysport (500 U; Ipsen Biopharm Ltd) administered according to a defined intramuscular injection algorithm. German and Austrian outpatient clinics. 516 male and female patients (aged ≥18 years) with de novo CD. The majority of patients had torticollis (78.1%). 35 patients had concomitant depression (MedDRA-defined). Change from baseline to weeks 4 and 12 in Craniocervical Dystonia Questionnaire (CDQ-24) total and subscale scores, patient diary items ('day-to-day capacities and activities', 'pain' and 'duration of pain') and global assessment of pain. Significant improvements were observed in CDQ-24 total and subscale scores at week 4 and were sustained up to week 12 (p<0.001). Changes in CDQ-24 scores did not significantly differ between the torticollis and laterocollis groups or between patients with or without depression. There were also significant reductions in patient diary item scores for activities of daily living, pain and pain duration at weeks 4 and 12 (p<0.001). Pain relief (less or no pain) was reported by 66% and 74.1% of patients at weeks 4 and 12, respectively. Changes in pain parameters demonstrated a positive relationship with change in Tsui score. After standardised open-label treatment with Dysport 500 U, improvements in QoL and pain intensity up to 12 weeks in patients with CD were observed.
    BMJ Open 01/2013; 3(4). · 1.58 Impact Factor
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Publication Stats

7k Citations
962.54 Total Impact Points


  • 2013
    • Deutsches Zentrum für Neurodegenerative Erkrankungen
      Bonn, North Rhine-Westphalia, Germany
  • 2012
    • University of Wuerzburg
      • Department of Neurology
      Würzburg, Bavaria, Germany
  • 1997–2012
    • University of Rostock
      • • Klinik und Poliklinik für Neurologie
      • • Zentrum für Nervenheilkunde
      Rostock, Mecklenburg-Vorpommern, 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
  • 1991–1992
    • 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
      Londinium, England, United Kingdom
  • 1980–1988
    • Georg-August-Universität Göttingen
      Göttingen, Lower Saxony, Germany