Klaus L Leenders

Klaus L Leenders
University of Groningen | RUG · Department of Developmental Neurology

About

426
Publications
32,884
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23,748
Citations
Citations since 2016
38 Research Items
6684 Citations
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201620172018201920202021202202004006008001,000
201620172018201920202021202202004006008001,000
Additional affiliations
March 1998 - present
University of Groningen
Position
  • Professor of Neurology

Publications

Publications (426)
Chapter
Medical therapy in de novo Parkinson’s disease typically starts with a dopamine agonist or levodopa in combination with a decarboxylase inhibitor or if symptoms are still very mild with a MAO-B inhibitor. When patients do not (or no longer) respond satisfactorily to these initial therapies, different drugs can be initiated or combined (i.e., “add-o...
Article
Background: Idiopathic rapid eye movement sleep behavior disorder (iRBD) represents the prodromal stage of α-synucleinopathies. Reliable biomarkers are needed to predict phenoconversion. Objective: The aim was to derive and validate a brain glucose metabolism pattern related to phenoconversion in iRBD (iRBDconvRP) using spatial covariance analys...
Article
Background and Objectives: 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with principal component analysis (PCA) has been applied to identify disease-related brain patterns in neurodegenerative disorders such as Parkinson’s disease (PD), Dementia with Lewy Bodies (DLB) and Alzheimer’s disease (AD). These patterns are used...
Article
Full-text available
Parkinson’s disease (PD) commences several years before the onset of motor features. Pathophysiological understanding of the pre-clinical or early prodromal stages of PD are essential for the development of new therapeutic strategies. Two categories of patients are ideal to study the early disease stages. Idiopathic rapid eye movement sleep behavio...
Article
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Background: Isolated rapid eye movement sleep behavior disorder (iRBD) is prodromal for α-synucleinopathies. Objective: The aim of this study was to determine whether pathological cardiac [123 I]meta-iodobenzylguanidine scintigraphy ([123 I]MIBG) is associated with progression of [18 F]fluorodeoxyglucose-positron emission tomography-based Parkin...
Article
Patients with isolated rapid-eye-movement sleep behaviour disorder (RBD) are commonly regarded as being in the early stages of a progressive neurodegenerative disease involving α-synuclein pathology, such as Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. Abnormal α-synuclein deposition occurs early in the neurodegenerat...
Chapter
Imaging of brain glucose metabolism with ¹⁸F-2-fluoro-2-deoxy-d-glucose positron emission tomography (¹⁸F-FDG PET) can give important information regarding disease-related changes in underlying neuronal systems, when combined with appropriate analytical methods. One such method is the scaled subprofile model combined with principal component analys...
Book
This book provides a comprehensive overview of the use of PET and SPECT in not only classic neurodegenerative disorders but also cerebrovascular disorders, brain tumors, epilepsy, head trauma, coma, sleeping disorders, and inflammatory and infectious diseases of the CNS. The new edition has been revised and updated to reflect recent advances and in...
Article
Full-text available
Background: Isolated rapid eye movement sleep behavior disorder is known to be prodromal for alpha-synucleinopathies, such as Parkinson's disease (PD) and dementia with Lewy bodies. The [18 F]fluorodeoxyglucose-positron emission tomography (PET)-based PD-related brain pattern can be used to monitor disease progression. Objective: We longitudinal...
Article
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Functional impairment of spatially distributed brain regions in Parkinson's disease (PD) suggests changes in integrative and segregative network characteristics, for which novel analysis methods are available. To assess underlying structural network differences between PD patients and controls, we employed MRI T1 gray matter segmentation and diffus...
Article
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It remains unclear whether the supportive imaging features described in the diagnostic criteria for progressive supranuclear palsy (PSP) are suitable for the full clinical spectrum. The aim of the current study was to define and cross-validate the pattern of glucose metabolism in the brain associated with a diagnosis of different PSP variants. A re...
Article
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Background and objective: Neurodegenerative diseases like Parkinson’s disease often take several years before they can be diagnosed reliably based on clinical grounds. Imaging techniques such as MRI are used to detect anatomical (structural) pathological changes. However, these kinds of changes are usually seen only late in the development. The mea...
Article
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Purpose Subthalamotomy using magnetic resonance–guided focused ultrasound (MRgFUS) has become a potential treatment option for the cardinal features of Parkinson’s disease (PD). The purpose of this study was to evaluate the effects of MRgFUS-subthalamotomy on brain metabolism using different scale levels. Methods We studied resting-state glucose m...
Article
Full-text available
Rationale In Parkinson’s disease (PD), spatial covariance analysis of ¹⁸F-FDG PET data has consistently revealed a characteristic PD-related brain pattern (PDRP). By quantifying PDRP expression on a scan-by-scan basis, this technique allows objective assessment of disease activity in individual subjects. We provide a further validation of the PDRP...
Article
Full-text available
Aim: L -3,4-dihydroxy-6-18F-fluorophenylalanine (18F-DOPA PET may be used to distinguish subjects with Parkinsonism from those with symptoms not originating from impaired dopaminergic transmission. However, it is not routinely utilized to discriminate Idiopathic Parkinson's disease (IPD) from Atypical Parkinsonian Disorders (APD). We investigated...
Article
Full-text available
Introduction: The implementation of spatial-covariance [18F]fluorodeoxyglucose positron emission tomography-based disease-related metabolic brain patterns as biomarkers has been hampered by intercenter imaging differences. Within the scope of the JPND-PETMETPAT working group, we illustrate the impact of these differences on Parkinson's disease-rel...
Article
Over the last years convolutional neural networks (CNNs) have shown remarkable results in different image classification tasks, including medical imaging. One area that has been less explored with CNNs is Positron Emission Tomography (PET). Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) is a PET technique employed to obtain a representat...
Article
Background/objective: Idiopathic REM sleep behavior disorder (iRBD) often precedes Parkinson's disease (PD) and other alpha-synucleinopathies. The aim of the study is to investigate brain glucose metabolism of patients with RBD and PD by means of a multidimensional scaling approach, using18F-FDG-PET as a biomarker of synaptic function. Methods:...
Chapter
Neuroimaging studies can provide in vivo insights to the early structural and functional brain changes in patients with idiopathic RBD (iRBD) and may help give a prognosis of disease course. This chapter summarizes the major findings of neuroimaging studies in iRBD, a specific prodromal stage of Parkinson’s disease (PD) and other α-synucleinopathie...
Article
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Introduction We aimed to uncover the pattern of network-level changes in neuronal function in Spinocerebellar ataxia type 3 (SCA3). Methods 17 genetically-confirmed SCA3 patients and 16 controls underwent structural MRI and static resting-state [¹⁸F]‑Fluoro‑deoxyglucose Positron Emission Tomography (FDG-PET) imaging. A SCA3-related pattern (SCA3-R...
Article
Rationale: Idiopathic REM sleep behavior disorder (iRBD) is considered a prodromal stage of Parkinson's disease (PD) and other Lewy-body disorders. Spatial covariance analysis of [18F]-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG-PET) data has disclosed a specific brain pattern of altered glucose metabolism in PD. In this study, we iden...
Conference Paper
Full-text available
Alzheimer's disease (AD) and Parkinson's disease (PD) are two common, progressive neurodegenerative brain disorders. Their diagnosis is very challenging at an early disease stage, if based on clinical symptoms only. Brain imaging techniques such as [ 18 F]-fluoro-deoxyglucose positron emission tomography (FDG-PET) can provide important additional i...
Article
Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify...
Article
The Patlak graphical analysis (PGAREF) for quantification of irreversible tracer binding with a reference tissue model was approximated by a dual time point imaging approach (DTPREF). The DTPREF was applied to 18 [(18)F]-FDOPA brain scans using the occipital cortex as reference region (DTPOCC) and compared to both PGAOCC and striatal-to-occipital r...
Article
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Parkinson’s disease is characterized not only by bradykinesia, rigidity, and tremor, but also by impairments of expressive and receptive linguistic prosody. The facilitating effect of music with a salient beat on patients’ gait suggests that it might have a similar effect on vocal behavior, however it is currently unknown whether singing is affecte...
Conference Paper
We apply Generalized Matrix Learning Vector Quantization (GMLVQ) to the classification of Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) brain data. The aim is to achieve accurate detection and discrimination of neurodegenerative syndromes such as Parkinson’s Disease, Multiple System Atrophy and Progressive Supranuclear Palsy. Image data...
Article
The current review focuses on recent human FDG-PET studies in Parkinson's disease. First, an overview is given of the current analytical approaches to metabolic brain imaging data. Next, we discuss how FDG-PET studies have advanced understanding of the relation between distinct brain regions and associated symptoms in Parkinson's disease, including...
Conference Paper
Objective: To compare the stepwise regression (SR) method and the decision tree (DT) method for classification of parkinsonian syndromes. Method: We applied the scaled subprofile model/principal component analysis (SSM/PCA) method to FDG-PET brain image data to obtain covariance patterns and the corresponding subject scores. The subject scores form...
Article
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Introduction: In this retrospective study concerning patients with Parkinson's disease (PD) scanned with 18-F-Dopa PET (N = 129), we looked for an association between reduced 18-F-Dopa uptake and the key PD symptoms tremor and hypokinesia-rigidity. We hypothesized to find a stronger correlation between dopaminergic depletion in the striatum and hyp...
Chapter
We apply Generalized Matrix Learning Vector Quantization (GMLVQ) and Support Vector Machine (SVM) classifiers to fluorodeoxyglucose positron emission tomography (FDG-PET) brain data in the hope to achieve better classification accuracies for parkinsonian syndromes as compared to the decision tree method which was used in previous studies. The class...
Article
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Several studies suggest different functional roles for the medial and the lateral sections of the ventral visual cortex in object recognition. Texture and surface information is processed in medial sections, while shape information is processed in lateral sections. This begs the question whether and how these functionally specialized sections inter...
Article
Objective DNAJC6 mutations were recently described in two families with autosomal recessive juvenile parkinsonism (onset age < 11), prominent atypical signs, poor or absent response to levodopa, and rapid progression (wheelchair-bound within ∼10 years from onset). Here, for the first time, we report DNAJC6 mutations in early-onset Parkinson's disea...
Article
Full-text available
We investigated simple directional hand movements based on different degrees of muscle co-activity, at behavioral and cerebral level in healthy subjects and Parkinson's disease (PD) patients. We compared "singular" movements, dominated by the activity of one agonist muscle, to "composite" movements, requiring conjoint activity of multiple muscles,...
Article
Full-text available
Cognitive deficits in Parkinson's disease (PD) have been associated with a specific metabolic covariance pattern. Although the expression of this PD cognition-related pattern (PDCP) correlates with neuropsychological performance, it is not known whether the PDCP topography is reproducible across PD populations. We therefore sought to identify a PDC...
Article
Full-text available
Medical imaging techniques like fluorodeoxyglucose positron emission tomography (FDG-PET) have been used to aid in the differential diagnosis of neurodegenerative brain diseases. In this study, the objective is to classify FDG-PET brain scans of subjects with Parkinsonian syndromes (Parkinson’s disease, multiple system atrophy, and progressive sup...
Article
Therapeutic options are limited in functional neurological paresis disorder. Earlier intervention studies did not control for a placebo effect, hampering assessment of effectivity. A proof-of-principle investigation was conducted into the therapeutic potential of repetitive transcranial magnetic stimulation (rTMS), using a single-blind two-period p...
Article
Full-text available
Corticobasal degeneration is an uncommon parkinsonian variant condition that is diagnosed mainly on clinical examination. To facilitate the differential diagnosis of this disorder, we used metabolic brain imaging to characterize a specific network that can be used to discriminate corticobasal degeneration from other atypical parkinsonian syndromes....
Article
Purpose: [(18)F]fluorodeoxyglucose (FDG) PET imaging of the brain can be used to assist in the differential diagnosis of dementia. Group differences in glucose uptake between patients with dementia and controls are well-known. However, a multivariate analysis technique called scaled subprofile model, principal component analysis (SSM/PCA) aiming a...
Article
Full-text available
Introduction Under normal conditions, the spatial distribution of resting cerebral blood flow and cerebral metabolic rate of glucose are closely related. A relatively new magnetic resonance (MR) technique, pseudo-continuous arterial spin labeling (PCASL), can be used to measure regional brain perfusion. We identified a Parkinson’s disease (PD)-rela...
Article
Full-text available
Objective: To assess whether standardized handwriting can provide quantitative measures to distinguish patients diagnosed with Parkinson's disease from age- and gender-matched healthy control participants. Design: Exploratory study. Pen tip trajectories were recorded during circle, spiral and line drawing and repeated character 'elelelel' and se...
Article
The clinical diagnosis of Huntington's disease (HD) is based on the motor symptoms, although these can be preceded by cognitive and behavioral changes. Biomarker studies have shown that structural imaging modalities are useful biomarkers of HD onset, while functional imaging measures have been studied less often for this purpose. Our aim was to inv...
Chapter
There have been a growing number of studies showing the importance of functional imaging studies using single-photon emission tomography (SPECT) or positron emission tomography (PET) tracers in neurology. In particular, Parkinson’s disease (PD) and other neurodegenerative disorders are useful disease models to understand the contribution of modern...
Chapter
Parkinson’s disease and parkinsonian disorders can present with a variety of symptoms, and there is often significant overlap between the different disorders. Diagnosis typically relies on clinical examination, especially at follow-up visits, which has limitations. Neuroimaging has played a major role in the elucidation of anatomical and functional...
Chapter
Full-text available
According to the limited amount of literature available, there is no real difference in diagnostic accuracy between a DaT-SPECT scan and an 18F-FDOPA PET scan nor between an123I-IBZM SPECT and a 11C-raclopride PET. However, while DaT-SPECT and FDOPA PET have gained a role in the clinical evaluation of the parkinsonian patient, especially in the dif...
Article
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Radial expanding optic flow is a visual consequence of forward locomotion. Presented on screen, it generates illusionary forward self-motion, pointing at a close vision-gait interrelation. As particularly parkinsonian gait is vulnerable to external stimuli, effects of optic flow on motor-related cerebral circuitry were explored with functional magn...
Article
In Parkinson's disease (PD), basal ganglia dysfunction leads to disturbed sensorimotor integration and associated timing. Previous functional MRI and behavioural PD studies on timing indicated a specific striatal contribution to assessing spatial displacement in velocity estimation. In this computation, cerebral processing time implies demarcating...
Article
Full-text available
The adenosine A2A receptor (A2AR) is highly concentrated in the striatum, and a therapeutic target for Parkinson's disorder (PD) and Huntington's disease. High affinity and selective radiolabeled A2AR antagonists can be important research and diagnostic tools for PD. Positron Emission Tomography (PET) can play an important role by measuring radiola...
Article
Full-text available
Background: The evaluation of effective disease-modifying therapies for neurodegenerative disorders relies on objective and accurate measures of progression in at-risk individuals. Here we used a computational approach to identify a functional brain network associated with the progression of preclinical Huntington's disease (HD). Methods: Twelve...
Article
Full-text available
The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophag...