Dorothée Lulé

Bio: Dorothée Lulé is an academic researcher from University of Ulm. The author has contributed to research in topics: Amyotrophic lateral sclerosis & Cognition. The author has an hindex of 34, co-authored 108 publications receiving 3277 citations. Previous affiliations of Dorothée Lulé include Medical University of Warsaw & University of Tübingen.

Neurofilaments in the diagnosis of motoneuron diseases: a prospective study on 455 patients

Abstract: Objectives Biomarkers for the diagnosis of motoneuron diseases (MND) are urgently needed to improve the diagnostic pathway, patient stratification and monitoring. The aim of this study was to validate candidate markers for MND in cerebrospinal fluid (CSF) and specify cut-offs based on large patient cohorts by especially considering patients who were seen under the initial differential diagnosis (MND mimics). Methods In a prospective study, we investigated CSF of 455 patients for neurofilament light chain (NfL), phosphorylated heavy chain (pNfH), tau protein (Tau) and phospho-tau protein (pTau). Analysed cohorts included patients with apparently sporadic and familial amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) (MND, n=253), MND mimics (n=85) and neurological control groups. Cut-off values were specified, and diagnostic performance and correlation with progression were analysed. Results Nfs were significantly higher in the MND group compared to the control groups, whereas Tau and pTau did not differ. At a cut-off level of 2200 pg/mL for NfL, a 77% diagnostic sensitivity (CI 71% to 82%), 85% specificity (CI 79% to 90%) and 87% positive predictive value (PPV) (CI 81% to 91%) were achieved. For pNfH, we calculated 83% sensitivity (CI 78% to 88%), 77% specificity (CI 71% to 83%) and 82% PPV (CI 77% to 86%) at 560 pg/mL. There were no significant differences between sporadic and genetic ALS or PLS. Nf levels were elevated at early disease stage, and correlated moderately with MND progression and duration. Conclusions Neurofilaments in CSF have a high relevance for the differential diagnosis of MNDs and should be included in the diagnostic work-up of patients. Their value as prognostic markers should be investigated further.

Global brain atrophy and corticospinal tract alterations in ALS, as investigated by voxel‐based morphometry of 3‐D MRI

Abstract: In ALS, advanced magnetic resonance imaging (MRI) techniques are increasingly used to investigate the underlying pathology. In this study, the technique of voxel-based morphometry (VBM) was applied to 3-D MRI data in ALS patients to localize regional grey and white matter changes. Twenty-two ALS patients (mean age 58+/-9 years) with clinically definite ALS by revised El Escorial criteria were studied. None of the patients had any signs of associated frontotemporal dementia. High-resolution 3-D MRI data sets of the whole brain, collected on a 1.5 T scanner, were analysed by statistical parametric mapping (SPM) and VBM in comparison to an age-matched normal data base consisting of 22 healthy volunteers (mean age 59+/-11 years), for grey matter and white matter segments separately. Global brain atrophy was assessed by calculation of brain parenchymal fractions (BPF). In ALS patients, BPF were significantly reduced compared to controls (p = 0.0003), indicating global brain atrophy. Regional decreases of grey matter density were found in the ALS patients at corrected p<0.01 in the right-hemispheric primary motor cortex (area of the highest Z-score) and in the left medial frontal gyrus. Furthermore, regional white matter alterations were observed along the corticospinal tracts bilaterally and in multiple smaller areas including corpus callosum, cerebellum, frontal and occipital subcortical regions. Besides considerable global atrophy in ALS, the topography of ALS-associated cerebral morphological changes could be mapped using VBM, in particular white matter signal changes along the bilateral corticospinal tracts, but also in extra-motor areas. VBM might be a potential tool to visualize disease progression in future longitudinal studies.

Life can be worth living in locked-in syndrome.

Abstract: The locked-in syndrome (LIS) describes patients who are awake and conscious but severely deefferented leaving the patient in a state of almost complete immobility and loss of verbal communication. The etiology ranges from acute (e.g., brainstem stroke, which is the most frequent cause of LIS) to chronic causes (e.g., amyotrophic lateral sclerosis; ALS). In this article we review and present new data on the psychosocial adjustment to LIS. We refer to quality of life (QoL) and the degree of depressive symptoms as a measure of psychosocial adjustment. Various studies suggest that despite their extreme motor impairment, a significant number of LIS patients maintain a good QoL that seems unrelated to their state of physical functioning. Likewise, depression is not predicted by the physical state of the patients. A successful psychological adjustment to the disease was shown to be related to problem-oriented coping strategies, like seeking for information, and emotional coping strategies like denial--the latter may, nevertheless, vary with disease stage. Perceived social support seems to be the strongest predictor of psychosocial adjustment. QoL in LIS patients is often in the same range as in age-matched healthy individuals. Interestingly, there is evidence that significant others, like primary caregivers or spouses, rate LIS patients' QoL significantly lower than the patients themselves. With regard to depressed mood, ALS patients without symptoms focus significantly more often on internal factors that can be retained in the course of the disease contrary to patients with depressive symptoms who preferably name external factors as very important, such as health, which will degrade in the course of the disease. Typically, ALS patients with a higher degree of depressive symptoms experience significantly less "very pleasant" situations. The herein presented data strongly question the assumption among doctors, health-care workers, lay persons, and politicians that severe motor disability necessarily is intolerable and leads to end-of-life decisions or euthanasia. Existing evidence supports that biased clinicians provide less-aggressive medical treatment in LIS patients. Thus, psychological treatment for depression, effective strategies for coping with the disease, and support concerning the maintenance of the social network are needed to cope with the disease. Novel communication devices and assistive technology now offers an increasing number of LIS patients to resume a meaningful life and an active role in society.

Diffusion tensor imaging analysis of sequential spreading of disease in amyotrophic lateral sclerosis confirms patterns of TDP-43 pathology.

Abstract: Diffusion tensor imaging can identify amyotrophic lateral sclerosis-associated patterns of brain alterations at the group level. Recently, a neuropathological staging system for amyotrophic lateral sclerosis has shown that amyotrophic lateral sclerosis may disseminate in a sequential regional pattern during four disease stages. The objective of the present study was to apply a new methodological diffusion tensor imaging-based approach to automatically analyse in vivo the fibre tracts that are prone to be involved at each neuropathological stage of amyotrophic lateral sclerosis. Two data samples, consisting of 130 diffusion tensor imaging data sets acquired at 1.5 T from 78 patients with amyotrophic lateral sclerosis and 52 control subjects; and 55 diffusion-tensor imaging data sets at 3.0 T from 33 patients with amyotrophic lateral sclerosis and 22 control subjects, were analysed by a tract of interest-based fibre tracking approach to analyse five tracts that become involved during the course of amyotrophic lateral sclerosis: the corticospinal tract (stage 1); the corticorubral and the corticopontine tracts (stage 2); the corticostriatal pathway (stage 3); the proximal portion of the perforant path (stage 4); and two reference pathways. The statistical analyses of tracts of interest showed differences between patients with amyotrophic lateral sclerosis and control subjects for all tracts. The significance level of the comparisons at the group level was lower, the higher the disease stage with corresponding involved fibre tracts. Both the clinical phenotype as assessed by the amyotrophic lateral sclerosis functional rating scale-revised and disease duration correlated significantly with the resulting staging scheme. In summary, the tract of interest-based technique allowed for individual analysis of predefined tract structures, thus making it possible to image in vivo the disease stages in amyotrophic lateral sclerosis. This approach can be used not only for individual clinical work-up purposes, but enlarges the spectrum of potential non-invasive surrogate markers as a neuroimaging-based read-out for amyotrophic lateral sclerosis studies within a clinical context.

Principles of Neural Science

Abstract: I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Plans and the Structure of Behavior

Abstract: which is used to describe a third component of thinking processes, particularly preverbal, and it denotes the concept that the world is activated by some generalized "energy" that links together causally all objects and events ; it is presumably revealed by a person's lack of curiosity about causal connections, as though they were self-evident. Aside from the rather frequent use of such key words, having strong connotations for this reviewer far away from what the author is aiming to denote, the book is written in a lucid and stimulating style that makes reading it an invigorating intellectual exercise. It is a book that is likely to have somewhat limited attraction to the full-time clinician, especially one treating adult patients. And child psychiatrists and psychologists, if reasonably well read, will most likely be familiar with the majority of references from which this author has synthesized his material. On the other hand, the scholarly and refreshing con¬ ceptual approaches of the author will appeal to psychologists, philosophers, linguists, and psychiatrists with a research bent and anyone else who wants to be provoked to do some thinking on the problems of language, language development, and the psychology of cognition. Louis A. GOTTSCHALK, M.D. Plans and the Structure of Behavior. By George A Miller, Eugene gALANTER, and Karl H. Pribram. Price, $5.00. Pp. 226. Henry Holt & Co., Inc., New York 17, 1960. This is an important book for psychiatrists and behavioral scientists, since it presents a clear, concise study of the application of cybernetics, information and computer theory to the problem of analyzing behavior. The authors have been actively engaged in behavioral research in different areas\p=m-\Millerin information and communication, Galanter in experimental psychology, and Pribram in neurophysiology. The book resulted from a series of discussions which they engaged in during a year they spent together at the Center for Advanced Study in the Behavioral Sciences, Palo Alto, Calif. Their original intent was to write a diary, as it were, of the development of their ideas and, fortunately, enough of this remains to make the book clear, easy to read, and interesting. It is also fortunate, however, that in the final writing a variety of studies comparing the "behavior" of computing machines with human "cognitive behavior" have been reviewed and summarized. The result is one of the best presentations of the present status of the brain-computer problem. The authors, however, do not discuss certain aspects of this problem, such as the difference between the brain and its vast number of parallel channels, but few operations, and the modern high-speed computer with its few channels and vast numbers of operations. This omission is consistent with their interest, since it would introduce the question of mechanisms rather than the problem of the structure of behavior as it is observed in everyday life in the clinic and in experiments on learning, conditioning, etc. Similarly, they do not discuss the qualitative differences between mechanisms of memory in the computer and those in the brain. In the former, a "memory"\p=m-\ i.e., stored information\p=m-\isidentified, metaphorically speaking, by an address, whereas no such mechanism is known in the brain (personal communication, Dr. Julian Bigelow). With few exceptions, however, the data, concepts, and theories presented are handled with elegant precision, as illustrated by the discussion of Sherrington's concepts of the "Reflex" and the "Synapse," Kurt Lewin's ideas of "tension states," and the numerous references to the work of Newell, Shaw, and Simon on computers and logic. There are, nevertheless, areas with