Abstracts and biosketches BCN Symposium 2017: Parallel session I

Drs. Marinus Oterdoom
Department of Neurosurgery
University Medical Center Groningen, the Netherlands

Trained as a neurosurgeon in the University Medical Center Groningen, drs. Marinus Oterdoom (1977) worked for five years in the Martini Hospital Groningen. In 2014, he rejoined the neurosurgical staff in the UMC Groningen and started specialization in spinal surgery and Deep Brain Stimulation (DBS). Together with professor Marc van Dijk (neurosurgeon) and professor Teus van Laar (neurologist) he now performs around 40 stereotactic procedures per year for treatment of movement disorders. Additionally, he participates in various research projects in this field, such as accuracy improvement in DBS implantation, as well as the search for cutting-edge indications for DBS (e.g. cognitive decline in Parkinson’s Disease and morbid obesity).

NBM stimulation as a target for cognitive sequalae in Parkinson’s Disease
The nucleus basalis of Meynert (NBM), located in the basal forebrain, emerges as a potential target of Deep Brain Stimualtion (DBS) for Parkinson’s disease dementia (PDD) and Alzheimer disease (AD). The NBM predominantly contains cholinergic neurons and serves an important role in cognition. In PD, and to a lesser extent in AD, the NBM progressively degenerates. This degeneration results in a decreased cholinergic input to the cortex. Preliminary evidence indicates that cholinergic input from the degenerating NBM might be enhanced by low-frequency (20 Hz) stimulation of the NBM. Furthermore, experimental evidence from rodents and preliminary human research indicates improved cognition after low-frequency stimulation of the NBM.

The possible role of the NBM as a potential target for cognitive improvement is under investigation.

Over the past three decades patients suffering from Parkinson’s Disease have been treated with DBS in the internal segment of the globus pallidus (GPi). This nucleus is located superior to the NBM and some patients may have been serendipitiously stimulated in the NBM. Anatomical position of patients who received  GPi DBS were evaluated and screened for cognitive changes in case of NBM stimulation (data analysis in progress).

Furthermore, in an initial attempt, exploratory measurement of local field potentials (LFP) was performed in two PDD patients with DBS electrodes implanted near the NBM. Also, NBM connectivity to cortical areas was investigated using simultaneous electroencephalography (EEG) recordings. Finally, a clinical trial in which DBS leads will be implanted in the NBM in PDD patients under preparation.

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Drs. Wieke Eggink

Department of Neurology
University Medical Center Groningen, the Netherlands

Wieke Eggink MSc (1988) obtained a bachelor degree in Human Movement Sciences and a master degree in Medicine at the University of Groningen (2104). Between 2014 and 2016 she worked as PhD student on her project entitled: ‘Moving forward in early-onset dystonia; a multidisciplinary approach to diagnosis and management’ at the department of neurology of the University Medical Center Groningen. Together with prof. dr. Marina de Koning-Tijssen she set up the multidisciplinary expert team for children en adults with dystonia and coordinated the care for deep brain stimulation in dystonia patients. In addition, she was involved with the organization of symposia and training schools in movement disorders for European young neurologists. She is currently working as neurology resident (ANIOS) at the department of neurology of the Isala Klinieken in Zwolle (NL).

Measuring the effectiveness of DBS in dystonia, a goal-oriented approach
Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive movements, postures or both. The broad range of possible etiologies of dystonia results in a heterogeneous patient population in terms of severity, distribution of symptoms and response to treatment.

Over the past decades, deep brain stimulation (DBS) has emerged as an important treatment option for patients with medically intractable dystonia. Efficacy studies reported beneficial results in primary (no anatomical lesion) dystonia whereas response in secondary (lesional) dystonia is highly variable, which leads to challenges in patient selection. Up to now effectiveness and primary outcome in studies is measured by the effect on motor symptoms. However, the severity of motor symptoms in dystonia patients is known to only fairly correlate with the perceived patients’ burden. Therefore, motor outcome might not adequately reflect the overall effect of DBS.

In our DBS-service, patients undergo a multidisciplinary screening pre- and postoperatively. This includes systematic assessment of motor and non-motor features. The main outcome measure is the reached amount of individual defined goals defined before the intervention. This approach provides an unique opportunity to get insights in patients’ motor and non-motor burden, expectations regarding the intervention and enables us to measure the effect of the therapy based on patient-oriented outcomes. Today, we present the DBS motor and goal-oriented outcomes of 14 dystonia patients treated with DBS at our center and discuss the strengths and limitations of this combined approach.

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Dr. Fiorella Contarino

Department of Neurology
University of Leiden, the Netherlands

Dr. M. Fiorella Contarino received her MD cum laude from the Università Cattolica del Sacro Cuore, in Rome, Italy, in 2000 with a dissertation entitled “Deep brain stimulation for the treatment of Parkinson’s disease”. In 2005 she obtained the degree of Neurologist at the same University. She then moved to The Netherlands and started working at the Academic Medical Centre (AMC) in Amsterdam, were she was appointed as researcher until 2016. In 2013 she received the PhD in Neuroscience at the University of Amsterdam, The Netherlands, with a dissertation entitled “DBS for movement disorders: toward an improvement of surgical treatment”.

Since 2012 she is working as clinical neurologist at the Haga Teaching Hospital in The Hague, The Netherlands and since 2016 she is also appointed as researcher at the Leiden University Medical Centre (LUMC), The Netherlands, combining clinical work and research in the field of movement disorders. Her main field of interest is the study of movement disorders, with a focus on neurostimulation approaches. She has been involved as co-investigator and principal investigator in clinical trials concerning deep brain stimulation for Parkinson’s disease, dystonia, and tremor, and the development of new technologies in the field of stereotactic surgery. She has also been involved in studies on new clinical applications of Botulinum toxin and development of new medications in the field of movement disorders. Furthermore, she contributed to the clinical characterization of patients with familial forms of dystonic syndromes and parkinsonism in the context of genetic studies.

In 2010 she was awarded the “Hans Speelman prize” on behalf of the Dutch Society for Functional Neurosurgery for Movement Disorders (NVFNB) for work in the field of DBS. She is regularly involved in national and international teaching activities on the topic of Movement Disorders and is responsible of an international DBS training in the DBS center of Haga Teaching Hospital/LUMC (YNLTP - Young Neurologists’ Training Program). She is member of the Medical Advisory Board of the Dutch Dystonia Patients Association (Dystonie Vereniging). Dr. M. Riorella Contarino has published more than 60 papers in peer-reviewed journals, and has an H-index of 21.

Furthermore she is Associate Editor of the journal Frontiers in Neurology - specialty session “Movement Disorders”, and is member of the review editorial board of the journal Parkinsonism and Related Disorders.

New technical advances in the field of DBS
In the past few years the field of Deep Brain Stimulation (DBS) has faced a tremendous wave of technological advances, and further steps are expected in the near future.

Progress has been made by introducing new modalities of stimulation, including larger ranges for the standard parameters (especially pulse width), or interleaved stimulation with different parameters applied to more than one electrode on the same lead. Thanks to the introduction of multiple source technology, vertical current steering is now available on some system, to allow shaping the stimulation field along the lead length. In addition, as alternative to the continuous stimulation, non-conventional stimulation modalities such as coordinated-reset stimulation are currently being tested.

The design of new leads containing smaller electrodes has made directional steering of stimulation possible. Some commercially available leads give the opportunity of stimulating through split contacts on 2 levels and 3 directions, in order to achieve larger therapeutic windows.

The introduction of new stimulation modalities implies also the broadening of stimulation possibilities, which can grow to the point of being difficult to be managed by the treating physician. Computational models of stimulation fields are currently being refined. In a near future these could be integrated in the stimulation systems to assist the physicians finding the optimal stimulation parameters for each patient.

Some implantable experimental system offer the possibility of recording brain activity form the same implanted stimulating lead in a chronic setting. This provides the possibility of studying neurophysiological markers correlated to different symptoms and conditions in daily life. This technology could offer the basis to adaptive stimulation, where recorded cell activity would drive on-demand stimulation patterns.
Finally, experimental projects are currently ongoing to further improve the comfort and usability of DBS hardware. These include the design of smaller Internal Pulse Generators, which could be implanted directly in the skull, and the set-up of systems of telemedicine to control and adjust stimulation parameters from a distance.

Conclusions
All new technologies provide potential improvement in the treatment of patients with DBS. However, the treating physicians will be constantly required to acquire new skills and competences involving computer interfaces, appliances, and stimulation modalities. Altogether, an increased level of complexity is observed which could produce the undesired effect of increasing the time needed for optimal programming, and further restricting the accessibility to these treatments. The challenge that the field is currently facing is to provide new technical advances that can, at the same time, offer the needed technological improvements without necessarily increase the complexity of management.

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Dr. Martijn Beudel
Department of Neurology
University Medical Center Groningen, the Netherlands

Martijn Beudel is a neurologist with a special interest in neuromodulation. He received his PhD in 2009 (cum laude) and finished his neurology training in 2016. During his post-doc in the UK (2014 -2015, University of Oxford and National Hospital for Neurology and Neurosurgery) he worked in the team of prof. Peter Brown on the development of a new adaptive form of DBS in Parkinson’s disease. Currently, he is funded by the Dutch Brain Foundation as a research-fellow and combines his clinical work with research on neuromodulation in movement disorders.

https://www.researchgate.net/profile/Martijn_Beudel

DBS: Mechanism of Action: From Paradoxes to New Insights and Techniques
Although DBS has been applied for more than 30 years in 2017, its mechanism of action remains controversial and breakthroughs have mostly been on an empirical basis. The most important advantage of this empirical approach is of course that clinically observed phenomena can be directly translated to improvements of the therapy. Its most important downside is, however, that it lacks the testing of hypotheses. By generating new hypotheses about the mechanism of action of DBS and test them, new insights and more sophisticated forms of stimulation could be developed.

In the current talk early and state-of art conceptions about the mechanism of action of DBS will be discussed in a chronological order. Next to this, the new opportunities derived from these new insights will be discussed. The scope will be restricted to the movement disorders Parkinson’s disease, tremor and dystonia.