Mark L. Kuijf

Prevalence of anxiety in Parkinson's disease: A systematic review and meta-analysis.

Prevalence rates of anxiety disorders in Parkinsons disease (PD) vary widely, ranging from 6% up to 55%. The aim of this systematic review was to calculate the average point prevalence of anxiety disorders and clinically relevant anxiety symptoms in PD.

Ultra-high field magnetic resonance imaging of the basal ganglia and related structures

Deep brain stimulation is a treatment for Parkinsons disease and other related disorders, involving the surgical placement of electrodes in the deeply situated basal ganglia or thalamic structures. Good clinical outcome requires accurate targeting. However, due to limited visibility of the target structures on routine clinical MR images, direct targeting of structures can be challenging. Non-clinical MR scanners with ultra-high magnetic field (7T or higher) have the potential to improve the quality of these images. This technology report provides an overview of the current possibilities of visualizing deep brain stimulation targets and their related structures with the aid of ultra-high field MRI. Reviewed studies showed improved resolution, contrast- and signal-to-noise ratios at ultra-high field. Sequences sensitive to magnetic susceptibility such as T2* and susceptibility weighted imaging and their maps in general showed the best visualization of target structures, including a separation between the subthalamic nucleus and the substantia nigra, the lamina pallidi medialis and lamina pallidi incompleta within the globus pallidus and substructures of the thalamus, including the ventral intermediate nucleus (Vim). This shows that the visibility, identification, and even subdivision of the small deep brain stimulation targets benefit from increased field strength. Although ultra-high field MR imaging is associated with increased risk of geometrical distortions, it has been shown that these distortions can be avoided or corrected to the extent where the effects are limited. The availability of ultra-high field MR scanners for humans seems to provide opportunities for a more accurate targeting for deep brain stimulation in patients with Parkinsons disease and related disorders.

Individualized parcellation of the subthalamic nucleus in patients with Parkinson's disease with 7T MRI

ABSTRACT Deep brain stimulation of the subthalamic nucleus (STN) is a widely performed surgical treatment for patients with Parkinsons disease. The goal of the surgery is to place an electrode centered in the motor region of the STN while lowering the effects of electrical stimulation on the non‐motor regions. However, distinguishing the motor region from the neighboring associative and limbic areas in individual patients using imaging modalities was until recently difficult to obtain in vivo. Here, using ultra‐high field MR imaging, we have performed a dissection of the subdivisions of the STN of individual Parkinsons disease patients. We have acquired 7 T diffusion‐weighted images of seventeen patients with Parkinsons disease scheduled for deep brain stimulation surgery. Using a structural connectivity‐based parcellation protocol, the STNs connections to the motor, limbic, and associative cortical areas were used to map the individual subdivisions of the nucleus. A reproducible patient‐specific parcellation of the STN into a posterolateral motor and gradually overlapping central associative area was found in all STNs, taking up on average 55.3% and 55.6% of the total nucleus volume. The limbic area was found in the anteromedial part of the nucleus. Our results suggest that 7T MR imaging may facilitate individualized and highly specific planning of deep brain stimulation surgery of the STN. HIGHLIGHTSThe subthalamic nucleus of individual Parkinson patients was parcellated at 7T MRI.A motor zone was found posterolaterally.Associative and limbic zones were found more anteriorly and anteromedially.A gradual overlap of the functional zones was found within the STN.

Factor analysis of the Hamilton Depression Rating Scale in Parkinson's disease

INTRODUCTION Several studies have validated the Hamilton Depression Rating Scale (HAMD) in patients with Parkinsons disease (PD), and reported adequate reliability and construct validity. However, the factorial validity of the HAMD has not yet been investigated. The aim of our analysis was to explore the factor structure of the HAMD in a large sample of PD patients. METHODS A principal component analysis of the 17-item HAMD was performed on data of 341 PD patients, available from a previous cross sectional study on anxiety. An eigenvalue ≥1 was used to determine the number of factors. Factor loadings ≥0.4 in combination with oblique rotations were used to identify which variables made up the factors. Kaiser-Meyer-Olkin measure (KMO), Cronbachs alpha, Bartletts test, communality, percentage of non-redundant residuals and the component correlation matrix were computed to assess factor validity. RESULTS KMO verified the samples adequacy for factor analysis and Cronbachs alpha indicated a good internal consistency of the total scale. Six factors had eigenvalues ≥1 and together explained 59.19% of the variance. The number of items per factor varied from 1 to 6. Inter-item correlations within each component were low. There was a high percentage of non-redundant residuals and low communality. CONCLUSION This analysis demonstrates that the factorial validity of the HAMD in PD is unsatisfactory. This implies that the scale is not appropriate for studying specific symptom domains of depression based on factorial structure in a PD population.

TREMOR12: An Open-Source Mobile App for Tremor Quantification

Background: Evaluating the effect of treatment of tremor is mostly performed with clinical rating scales. Mobile applications facilitate a more rapid, objective, and quantitative evaluation of treatment effect. Existing mobile apps do not offer raw data access, which limits algorithm development. Objective: To develop a novel open-source mobile app for tremor quantification. Methods: TREMOR12 is an open-source mobile app that samples acceleration, rotation, rotation speed, and gravity, each in 3 axes and time-stamped in a frequency up to 100 Hz. The raw measurement data can be exported as a comma-separated value file for further analysis in the TREMOR12P data processing module. The app was evaluated with 3 patients suffering from essential tremor, who were between 55 and 71 years of age. Results: This proof-of-concept study shows that the TREMOR12 app is able to detect and register tremor characteristics such as acceleration, rotation, rotation speed, and gravity in a simple and nonburdensome way. The app is compatible with current regulatory oversight by the European Union (MEDDEV regulations) and the Food and Drug Administration (FDA) guidance on mobile medical applications. Conclusion: TREMOR12 offers low-cost tremor quantification for research purposes and algorithm development, and may help to improve treatment evaluation.

Unraveling the Relationship between Motor Symptoms, Affective States and Contextual Factors in Parkinson's Disease: A Feasibility Study of the Experience Sampling Method.

Background In Parkinsons disease (PD), the complex relationship between motor symptoms, affective states, and contextual factors remains to be elucidated. The Experience Sampling Method provides (ESM) a novel approach to this issue. Using a mobile device with a special purpose application (app), motor symptoms, affective states and contextual factors are assessed repeatedly at random moments in the flow of daily life, yielding an intensive time series of symptoms and experience. The aim of this study was to study the feasibility of this method. Method We studied the feasibility of a five-day period of ESM in PD and its ability to objectify diurnal fluctuations in motor symptom severity and their relation with affect and contextual factors in five PD patients with motor fluctuations. Results Participants achieved a high compliance, with 84% of assessment moments completed without disturbance of daily activities. The utility of the device was rated 8 on a 10-point scale. We were able to capture extensive diurnal fluctuations that were not revealed by routine clinical assessment. In addition, we were able to detect clinically relevant associations between motor symptoms, emotional fluctuations and contextual factors at an intra-individual level. Conclusions ESM represents a viable and novel approach to elucidate relationships between motor symptoms, affective states and contextual factors at the level of individual subjects. ESM holds promise for clinical practice and scientific research.

Ultra-High Field MRI Post Mortem Structural Connectivity of the Human Subthalamic Nucleus, Substantia Nigra, and Globus Pallidus

Introduction: The subthalamic nucleus, substantia nigra, and globus pallidus, three nuclei of the human basal ganglia, play an important role in motor, associative, and limbic processing. The network of the basal ganglia is generally characterized by a direct, indirect, and hyperdirect pathway. This study aims to investigate the mesoscopic nature of these connections between the subthalamic nucleus, substantia nigra, and globus pallidus and their surrounding structures. Methods: A human post mortem brain specimen including the substantia nigra, subthalamic nucleus, and globus pallidus was scanned on a 7 T MRI scanner. High resolution diffusion weighted images were used to reconstruct the fibers intersecting the substantia nigra, subthalamic nucleus, and globus pallidus. The course and density of these tracks was analyzed. Results: Most of the commonly established projections of the subthalamic nucleus, substantia nigra, and globus pallidus were successfully reconstructed. However, some of the reconstructed fiber tracks such as the connections of the substantia nigra pars compacta to the other included nuclei and the connections with the anterior commissure have not been shown previously. In addition, the quantitative tractography approach showed a typical degree of connectivity previously not documented. An example is the relatively larger projections of the subthalamic nucleus to the substantia nigra pars reticulata when compared to the projections to the globus pallidus internus. Discussion: This study shows that ultra-high field post mortem tractography allows for detailed 3D reconstruction of the projections of deep brain structures in humans. Although the results should be interpreted carefully, the newly identified connections contribute to our understanding of the basal ganglia.

Is there still need for microelectrode recording now the subthalamic nucleus can be well visualized with high field and ultrahigh MR imaging

Citation: Kocabicak E, Alptekin O, Ackermans L, Kubben P, Kuijf M, Kurt E, Esselink R and Temel Y (2015) Is there still need for microelectrode recording now the subthalamic nucleus can be well visualized with high field and ultrahigh MR imaging? Front. Integr. Neurosci. 9:46. doi: 10.3389/fnint.2015.00046 Is there still need for microelectrode recording now the subthalamic nucleus can be well visualized with high field and ultrahigh MR imaging?

Modeling anxiety in Parkinson's disease

The aim of this work was to construct a model for anxiety in PD and compare the relative contributions of PD‐specific and ‐nonspecific general population risk factors for anxiety in this model.

A detailed analysis of intracerebral hemorrhages in DBS surgeries

OBJECTIVES Deep brain stimulation is nowadays a frequently performed surgery in patients with movement disorders, intractable epilepsy, and severe psychiatric disorders. The most feared complication of this surgery is an intracerebral hemorrhage due to the electrode placement, either for intraoperative electrophysiology (microelectrode recording) and/or implantation of the final electrode (macroelectrode). Here, we have investigated the risk of developing an intracerebral hemorrhage in our cohort of deep brain stimulation patients over a period of 15 years. PATIENTS AND METHODS We have collected demographic data and analyzed the effect of performing surgery with single-electrode versus multiple electrode guided DBS. The effect of using single-dose versus double-dose contrast enhanced MRI to visualize vessels for the electrode trajectory planning has been investigated as well. RESULTS We have found that the overall calculated risk of an intracerebral hemorrhage in our series was 1.81% per patient, 0.3% per recording electrode and 0.23% per brain insertion. While three out of four patients recovered without neurological deficits, there was one mortality in a patient with cardiovascular comorbidities. Statistical comparisons between the groups of single-electrode versus multiple electrode guided surgery and single-dose gadolinium versus double-dose contrast enhanced MRI revealed no significant differences. In addition, there was no meaningful correlation between the age at surgery and the risk of bleeding. CONCLUSION We have found that the risk of developing an intracerebral hemorrhage due to deep brain stimulation surgery is low. The clinical course of the patients with an intracerebral hemorrhage was generally favorable.