Peter Trillenberg

• Universitätsklinikum Schleswig - Holstein

Background/aim: Standard radiotherapy (RT) for glioblastoma lasts 6 weeks. We aimed to identify patients who would benefit from a hypofractionated approach. Patients and methods: In 167 patients receiving standard fractionation, 10 factors were analyzed for local control (LC) and overall survival (OS). A survival score was developed and compared...

Background/aim: A recommendation of radiotherapy for patients with malignant gliomas may trigger emotional distress. Frequency and risk factors of this complication were investigated. Patients and methods: Prevalence of six emotional problems and 11 potential risk factors were evaluated in 103 patients irradiated for grade II-IV gliomas. p-Value...

Purpose: As measures of association between an adverse drug reaction (ADR) and exposure to a drug the reporting odds ratio (ROR) and the information component (IC) can be used. We sought to test the reliability of signal detection with these. Methods: We simulated ADR counts as binomially distributed random numbers for different expected ADR fre...

Background/aim: Little is known regarding seizures during radiotherapy for brain tumors. This prospective study investigated seizure activity in patients irradiated for high-grade gliomas. Patients and methods: Using a seizure diary, progression of seizure activity was evaluated in 22 patients receiving chemoradiation for grade III (n=1) or IV (...

Objective: The head impulse test (HIT) assesses the vestibulo-ocular reflex (VOR) and is used to differentiate vestibular neuritis (abnormal VOR) from stroke (normal VOR) in patients presenting with an acute vestibular syndrome (AVS). The video-oculography-based HIT (vHIT) quantifies VOR function and provides information imperceptible for the clini...

Background Some groups of cardiovascular drugs (beta blocking drugs, Ca antagonists, antiarrhythmics) are listed as potentially worsening myasthenia. An empirical basis for alternative recommendations for antihypertensive and antiarrhythmic therapy in myasthenia patients has not yet been provided. Methods From the World Health Organization pharmac...

Background Gliomas are often associated with symptoms including seizures. Most patients with high-grade gliomas are treated with radiotherapy or radio-chemotherapy. Since irradiation causes inflammation, it may initially aggravate symptoms. Studies focusing on seizure activity during radiotherapy for gliomas are not available. Such knowledge may im...

Background Many drugs can worsen myasthenia symptoms. The clinician usually relies on cautionary lists compiled according to case reports. We intended to provide a quantitative basis for a risk comparison within the groups of antiepileptic, antidepressant, neuroleptic and sedative drugs. Methods From the WHO pharmacovigilance database we extracted...

Background/aim: In a previous study investigating radiotherapy for newly diagnosed glioblastoma multiforme (GBM), significant or almost significant associations with survival were found for performance status, upfront resection, O6-methylguanine-DNA methyl-transferase (MGMT) promoter methylation and unifocal GBM. This study aimed to create a survi...

Intravenous thrombolysis (IVT) is rarely performed in dizzy patients with acute vestibular syndrome (AVS) or acute imbalance (AIS) even if posterior circulation stroke (PCS) is suspected. Decision-making may be affected by uncertainties in discriminating central from peripheral vestibulopathy or concerns of IVT-related harm, particularly intracereb...

Objective The bedside head impulse test (bHIT) is used to differentiate vestibular neuritis (VN) from posterior circulation stroke (PCS) in patients presenting with acute vestibular syndrome (AVS). If assessed by neuro‐otological experts, diagnostic accuracy is high. We report on its diagnostic accuracy, when applied by non‐experts during routine c...

The usefulness of brain imaging studies in dizzy patients presenting to the emergency department (ED) is controversial. We aimed to assess the ‘real-world’ probability of ischemic stroke and other acute brain lesions (ABLs) in these patients to create an algorithm that helps decision-making on whether which and when brain imaging is needed. By revi...

Smooth pursuit eye movements (SPEM), optokinetic nystagmus (OKN) and the vestibular ocular reflex (VOR) enable us to focus our eyes constantly on objects that move relative to us. In real life situations, natural stimuli that elicit SPEM, OKN and the VOR are processed simultaneously, and do not always act synergistically.

Due to the elliptic shape of Earth's orbit around the Sun, the apparent diameter of the Sun varies throughout the year. With digital analysis of a number of images at a given date, the effect can be demonstrated with a digital single lens reflection camera (DSLR) and a standard telephoto lens even over a few days. In the analysis, the influence of...

Despite many reports on visual processing deficits in psychotic disorders, studies are needed on the integration of visual and non-visual components of eye movement control to improve the understanding of sensorimotor information processing in these disorders. Non-visual inputs to eye movement control include prediction of future target velocity fr...

Objective Our aim was to identify the role of the investigators’ knowledge of the patient’s history of vestibular symptoms (PVH) in the clinical evaluation of the bedside head-impulse test (bHIT). We hypothesized that this knowledge will reduce uncertainty and improve bHIT accuracy when compared to quantitative analysis of the vestibulo-ocular refl...

Objective: Antibodies to cell surface central nervous system proteins help to diagnose conditions which often respond to immunotherapies. The assessment of antibody assays needs to reflect their clinical utility. We report the results of a multicentre study of aquaporin (AQP) 4 antibody (AQP4-Ab) assays in neuromyelitis optica spectrum disorders (...

Introduction: Transcranial electrical stimulation (TES) is a set of methods for the non-invasive electrical stimulation of the brain, including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS). With the help of multi-channel stimulation setups, it is possible to stimulate focally by applying cur...

Introduction: Transcranial alternating current stimulation (tACS) is an emerging tool for modulating brain oscillations. Recent research theoretically proved the possibility of focal stimulation using multi-channel tACS setups. However, the step from simulation to reality is still missing. Existing multi-channel systems feature a low number of chan...

Schwindel zählt zu den häufigsten Symptomen, die Patienten in Deutschland zum Arzt führen. Die Diagnosestellung basiert auf einer gezielten Anamnese, klinischen Untersuchung und sinnvollen Zusatzdiagnostik. Zum Nachweis oder Ausschluss einer vestibulären Unterfunktion als Ursache des Schwindels kamen bisher v. a. die kalorische Erregung des Gleichg...

Smooth pursuit eye movements (SPEM) and saccades are the 2 basic modes of eye movements. SPEM have their optimal velocity range below 30°/s, much slower than saccades. They are needed for visual discrimination of moving objects, by adjusting eye velocity to target velocity. This requires an exact visuo-motor coordination by integrating visual feeed...

Dizziness is one of the most common complaints in Germany which leads to medical consultation. Diagnosis is based on patient history, clinical examination and laboratory tests. In order to find or exclude a vestibular lesion, methods such as caloric irrigation, rotational chair tests or vestibular-evoked myogenic potentials were previously applied....

We study the impact of coil orientation on the motor threshold (MT) and present an optimal coil orientation for stimulation of the foot. The result can be compared to results of models that predict this orientation from electrodynamic properties of the media in the skull and from orientations of cells, respectively. We used a robotized TMS system f...

S1: More detailed quantitative data of smooth pursuit parameters. Supplementary material 1

Background: Neurological and psychiatric disorders show clinical overlap suggesting a shared pathophysiological background. We evaluated myoclonus-dystonia, a monogenic movement disorder as a disease model for inherited psychopathology. Method: We investigated 12 SGCE mutation carriers using standardized neurological and psychiatric examinations...

Electrooculography is a method to record eye movements using the corneoretinal potential. A calibration is required to find the relation between eye position and signal. With this relation impairments of the oculomotor and the vestibular system can be described quantitatively.

The quantification of stimulation intensity in transcranial magnetic stimulation (TMS) as a function of depth is of interest in order to adjust stimulator output when non-motor regions are stimulated. Currently, a linear increase of stimulator output to correct for depth has been suggested. This is contrary to the physical properties of the electri...

Evidence exists that modulation of neuronal activity in nucleus accumbens shell region may re-establish normal function in various neuropsychiatric conditions such as drug-withdrawal, obsessive-compulsive disorder, depression and chronic pain. Here, we study the effects of acute repetitive transcranial magnetic stimulation on monoamine outflow in t...

Patients with Parkinson's disease (PD) have difficulties in the control of self-guided (i.e., internally driven) movements. The basal ganglia provide a nonspecific internal cue for the development of a preparatory activity for a given movement in the sequence of repetitive movements. Controversy surrounds the question of whether PD patients are cap...

Background: Transcranial Magnetic Stimulation (TMS) is based on a changing magnetic field inducing an electric field in the brain. Conventionally, the TMS coil is mounted to a static holder and the subject is asked to avoid head motion. Additionally, head resting frames have been used. In contrast, our robotized TMS system employs active motion co...

Alterations in sensorimotor processing and predictive mechanisms have both been proposed as the primary cause of eye tracking deficits in schizophrenia. 20 schizophrenia patients and 20 healthy controls were assessed on blocks of predictably moving visual targets at constant speeds of 10, 15 or 30°/s. To assess internal drive to the eye movement sy...

In everyday life while shifting our gaze to objects of interest, our eyes are highly conjugated (Hering’s law, 1868). It is unknown whether binocular control is active during human REM sleep. Monkey REM sleep eye movements could be observed that did not follow Hering’s law. Recent human electrophysiological and functional imaging studies indicate a...

Externally guided sensory-motor processes deteriorate with increasing age. Internally guided, for example, predictive, behavior usually helps to overcome sensory-motor delays. We studied whether predictive components of visuomotor transformation decline with age. We investigated smooth pursuit eye movements (SPEM) of 45 healthy subjects with paradi...

Thrombolysis is a dynamic and time-dependent process influenced by the haemodynamic conditions. Currently there is no model that allows for time-continuous, non-contact measurements under physiological flow conditions. The aim of this work was to introduce such a model. The model is based on a computer-controlled pump providing variable constant or...

Navigated and robotized Transcranial Magnetic Stimulation (TMS) is advancing forward in research and treatment. MRI-scans or other medical image data are typically used as navigation source. Unfortunately, scanning time is always short and expensive. For many TMSapplications the underlying brain topology is not necessarily needed. Therefore, we gen...

Introduction: For transcranial magnetic stimulation (TMS) precise positioning of the stimulation coil is required. In clinical routine ‘standard’ coil orientations are used. Studies investigating the optimal coil orientation have been very coarse. The most detailed studies addressed the hand region, with rotation steps as large as 45°. For the stim...

This chapter discusses that the testing of ocular motor functions is an important step in the diagnosis of vestibular and balance disorders for three reasons: First, most of these disorders are associated with the disorders of eye movements. Second, the classification of the eye movement disorder will often lead to localization of the neural struct...

Diese Ubersicht soll helfen, anhand von anamnestischen Angaben und klinischen Befunden syndromal eine klinisch zutreffende Schwindel Diagnose zu stellen, die nur in geringerer Anzahl durch apparative Untersuchungen bestatigt werden muss. This review is intended to assist in making a syndromal diagnosis of vertigo on the basis of details from the ca...

Introduction: It has been shown that fibrillations (FIBs) and positive sharp waves (PSWs) occur during spontaneous oscillations of the membrane potential when the threshold is reached. According to the models of excitable membranes these oscillations should be nonlinear. We wondered whether the nonlinearity of the underlying process could also be d...

Transcranial magnetic stimulation provides a mean to stimulate the brain non-invasively and painlessly. The effect of the stimulation hereby depends on the stimulation coil used and on its placement. This paper presents a mapping algorithm based on the assumption of a monotonous functional relationship between the applied electric field strength at...

Smooth pursuit eye movements enable us to focus our eyes on moving objects by utilizing well-established mechanisms of visual motion processing, sensorimotor transformation and cognition. Novel smooth pursuit tasks and quantitative measurement techniques can help unravel the different smooth pursuit components and complex neural systems involved in...

Introduction: Regularity is assumed to be the definitive criterion to distinguish fibrillation potentials and positive sharp waves from other forms of electrical activity in resting muscle. In clinical routine regularity is established acoustically. We wanted to determine the threshold for examiners to detect irregularity in spike trains. Methods:...

Visually evoked flow characterises the relative changes of blood flow velocity in the posterior cerebral artery in response to visual stimulation. The present study is the first to address the reliability of model fitting to evoked flow responses, rigorously defined by Cronbach's alpha. We fitted two models to the evoked flow responses recorded fro...

The posterior parietal cortex (PPC) is essential for the integration of visuomotor information during visually guided reaching. Studies in macaque monkeys have demonstrated a functional specialisation around the intraparietal sulcus (IPS) with a more medial representation of hand movements ("parietal reach region") and a more lateral representation...

In obsessive-compulsive disorder (OCD), a dysfunction of neuronal circuits involving prefrontal areas and the basal ganglia is discussed that implies specific oculomotor deficits. Performance during reflexive and predictive saccades, antisaccades and predictive smooth pursuit was compared between patients with OCD (n=22), patients with schizophreni...

This paper describes the setup and first applications of a computer-aided robotized Transcranial Magnetic Stimulation (TMS) system for motion compensated brain stimulation The system uses a registration of the cranium to its 3D magnetic resonance imaging (MRI) data and constant infrared stereo optical tracking to establish a real-time link between...

We investigated a five-year-old girl suffering from genetically confirmed, action-induced myoclonus-dystonia (M-D) with functional magnetic resonance imaging (MRI). We compared the activation pattern by movements of her right hand as if drawing a picture, which elicited M-D, with simple snapping movements (without overt M-D). The drawing and snappi...

Patients with essential tremor (ET) or with cerebellar lesions have in common oculomotor abnormalities, with the exception of saccadic eye movements, which do not seem to be involved in ET. Since grasping is prolonged in ET and might be related to saccadic dysmetria, we tested whether simultaneous hand pointing could unmask it. Twelve ET patients a...

Hypersalivation is frequently observed in patients treated with clozapine. Current strategies to counteract sialorrhea include the introduction of antimuscarinergic (anticholinergic) and alpha(2)-agonistic treatment. However, the use of these substances is limited in part by lack of efficacy and by adverse side effects. In cases of intractable sial...

In schizophrenia, affective disorders, and obsessive-compulsive disorder (OCD) dysfunction of frontal neuronal circuits has been suggested. Such impairments imply corresponding oculomotor deficits. Eye movement response to foveofugal and foveopetal step-ramp stimuli was recorded within the same study design in patients with schizophrenia (N= 16), a...

Hypersalivation is a common and frequently disabling side effect of atypical neuroleptics such as clozapine. Current treatment options of this adverse advent are limited by lack of efficacy or additional side effects. Botulinum toxin (BTX) injections into the parotid glands have been shown to be very effective in treating sialorrhea in the context...

During the past year a number of studies have been published on eye movement dysfunction in patients with psychiatric disease. According to the mainstream of modern neuropsychiatric research, these studies cover either genetic aspects or the results of pharmacological manipulation. A few studies addressed impaired smooth pursuit eye movements (eye...

Patients with degenerative cerebellar disease were compared to healthy controls in their ability to adapt behaviour to temporal contingencies, both according to instructions and according to acquired experience. Participants had to press the cued key whenever the inside of a clock face changed its colour, which could occur when the pointer, rotatin...

The three pairs of semicircular canals within the labyrinth are not perfectly aligned with the pulling directions of the six extraocular muscles. Therefore, for a given head movement, the vestibulo-ocular reflex (VOR) depends upon central neural mechanisms that couple the canals to the muscles with the appropriate functional gains in order to gener...

Histograms of fast-phase intervals in human optokinetic and vestibular nystagmus were generated, and fitted to statistical distributions used in previous studies. The distributions did not depend on stimulation type (optokinetic or vestibular). An inverse Gaussian or a gamma distribution fitted the data better than did a reciprocal Gaussian distrib...

Optokinetic nystagmus (OKN) is a reflexive eye movement with target-following slow phases (SP) alternating with oppositely directed fast phases (FP). We measured the following from OKN in three humans: FP beginning and ending positions, amplitudes, and intervals and SP amplitudes and velocities. We sought to predict future values of each parameter...

Recent research from our laboratory has been directed at understanding the range of capabilities for adaptive control of eye movements in normal human subjects. For smooth pursuit, different motor responses to the same sensory stimulus (horizontal target motion) can be learned, stored and gated in or out, according to context (vertical eye position...

To assess the potential significance of Epstein-Barr virus (EBV) reactivation in disease activity in MS patients. The prevalence of antibodies against herpes simplex virus type 1 (HSV-1), HSV-2, EBV, and cytomegalovirus was determined in a group of 108 MS patients and in 163 healthy control subjects. Sera were analyzed using combinations of novel a...

Uncertainty about the timing of a known external event is an everyday phenomenon but has been rarely investigated with electrophysiological methods. We studied how the amplitude of the contingent negative variation (CNV) is affected by temporal variation of S2 presentation. Competing hypotheses about the development of CNV during the foreperiod unt...

The late part of the Contingent Negative Variation (CNV) is assumed to be a composite potential, reflecting both movement preparation and several other processes. To assess the contribution of hand-motor preparation to overall CNV, three S1-S2 experiments were performed. Replicating earlier results that have been interpreted as demonstrating hand-m...

It is well known that cerebellar dysfunction can lead to an impairment of eye velocity during sustained pursuit tracking of continuously moving visual target. We have now studied the initiation of smooth pursuit eye movements towards predictable and randomized visual step-ramp stimuli in six patients with degenerative cerebellar lesions and six age...

The clinical and molecular findings in three patients with multiple sclerosis (MS) and additional type 1 diabetes mellitus are described. These patients all presented with a severe and progressive disease course of MS. Molecular testing for HLA class II genes demonstrated the presence of the haplotype DRB1*0401, DQB1*0302 in all patients. This hapl...

The cerebellum is certainly involved in fine coordination of movements, but has no efferences of its own to the muscles. Thus, it can exert its influence only via other cerebral areas that have those efferences. This study investigated in patients with cerebellar atrophy how cortical motor areas are affected by dysfunction of the cerebellum. The ma...

The clinical and molecular findings in three patients with multiple sclerosis (MS) and additional type 1 diabetes mellitus are described. These patients all presented with a severe and progressive disease course of MS. Molecular testing for HLA class II genes demonstrated the presence of the haplotype DRB1∗0401, DQB1∗0302 in all patients. This hapl...

Repeated presentation of a continuously moving visual target can elicit two types of smooth eye movements that can be identified by their time of onset (Kao and Gellman 1994). One type builds up well before the target motion appears and represents an anticipatory smooth eye movement (ASEM) that is solely driven by predictive expectations derived fr...

Transcranial magnetic stimulation (TMS) was used to study intracortical inhibitory and excitatory phenomena in patients with cerebellar ataxia. Motor evoked potentials (MEP) following single and paired TMS were recorded from the first dorsal interosseus muscle (FDI) in 15 patients with autosomal-dominant or idiopathic cerebellar ataxia and 15 age m...

To investigate the in vivo effect of corticosteroid pulse therapy on immunocompetent cells in 18 patients given methylprednisolone to treat an acute episode of MS. Blood was sampled before and after 3 days of methylprednisolone administration at doses of 1 g/day. Lymphocyte subtyping was performed and whole blood cell cultures were used to measure...

A reduced gain of smooth pursuit eye velocity has frequently been reported in schizophrenic patients. With respect to predictable stimuli, this could be due to a deficit in predicting the target path. To determine this contribution to smooth pursuit eye movement performance, we analyzed the ocular smooth pursuit response to a sinusoidally moving ta...

We add evidence from functional imaging supporting the concept of activation of coronally oriented zones corresponding to parallel fibers. Braitenberg et al.'s suggestion that there is an operating mode of the cerebellum relies on the idea introduced by Eccles and refined by the concept of tidal waves which Heck found in vitro. Recent evidence...

This paper presents a refined asymptotic expansion for the partition function Θ(t)=Tr etΔ of quantum billiards in the unbounded regions {0≤x,0≤yxμ≤1}, μ>0, and {0≤ye‖x‖≤1}⊆R2, where Δ is the Dirichlet Laplacian. Simon [Ann. Phys. 146, 209 (1983); J. Funct. Anal. 53, 84 (1983)] determined the leading divergence of the trace of the heat kernel for th...