Dorothée Lulé

University and rehabilitation clinics Ulm

Purpose Amyotrophic lateral sclerosis (ALS) is a progressive motor impairment leading to early death. Religiousness is one of the factors potentially alleviating the psychological burden of patients. However, its role might vary according to cultural context. Our study aimed to analyze religiosity, and its clinical, psychological and socio-demograp...

Spinal muscular atrophy (SMA) is a disabling disease that affects not only the patient’s health-related quality of life (HRQoL), but also causes a high caregiver burden (CGB). The aim of this study was to evaluate HRQoL, CGB, and their predictors in SMA. In two prospective, cross-sectional, and multi-center studies, SMA patients (n = 39) and SMA pa...

Objective: To analyze the quality of life (QoL) and frequency of depression in primary caregivers of patients with amyotrophic lateral sclerosis (ALS) in two neighboring European countries. Methods: a cross-sectional study performed in 164 dyads of ALS patients and caregivers followed at clinical ALS centers in Poland and Germany between 2015 and 2...

Objective: To investigate intercultural neurologists' perception of well-being in patients with amyotrophic lateral sclerosis (ALS) using gastrostomy (PEG), non-invasive, and/or invasive ventilation (NIV/IV) and to analyse the determinants and impact on the management of the above medical interventions (MIs). Methods: The study was based on anon...

Introduction Diffusion tensor imaging (DTI) can be used to map disease progression in amyotrophic lateral sclerosis (ALS) and therefore is a promising candidate for a biomarker in ALS. To this end, longitudinal study protocols need to be optimized and validated regarding group sizes and time intervals between visits. The objective of this study was...

Objective: The goal of this meta-analysis is to improve insight into the development of cognition over the course of ALS and to assess predictors of cognitive performance. Method: A literature search was conducted in Pubmed and Web of Science on 29 July 2019 and 16 March 2021. Data were screened in Endnote® Version X9 (London, UK). Meta-analyses an...

Background and objective: Diffusion tensor imaging (DTI) can be used to tract-wise map correlates of the sequential disease progression and, therefore, to assess disease stages of amyotrophic lateral sclerosis (ALS) in vivo. According to a threshold-based sequential scheme, a classification of ALS patients into disease stages is possible, however,...

Background: The underlying neuropathological process of amyotrophic lateral sclerosis (ALS) can be classified in a four-stage sequential pTDP-43 cerebral propagation scheme. Using diffusion tensor imaging (DTI), in vivo imaging of these stages has already been shown to be feasible for the specific corticoefferent tract systems. Because both cognit...

Introduction: The neuropathological process underlying amyotrophic lateral sclerosis (ALS) can be classified as a four-stage propagation scheme. An in vivo transfer of these stages using diffusion tensor imaging (DTI) in specific tract systems has been established [1]. Since cognitive functions are closely linked to microstructural changes, an anal...

Objective To investigate the association between neuropsychological deficits and psychological well-being in amyotrophic lateral sclerosis (ALS). Methods Subjective (Schedule for the Evaluation of the Individual Quality of Life-Direct Weighting, SEIQoL-DW) and global quality of life (QoL; Anamnestic Comparative Self-Assessment, ACSA) as well as de...

Background Spinal muscular atrophy (SMA) issues from mutations in the survival of motor neuron (SMN) 1 gene. Loss or reduction of the SMN protein results in progressive muscle weakness. Whether this protein deficiency also affects cortical function remains unclear. While no data on adult patients exists so far, prior studies in children with SMA in...

Objective ALS primarily affects motor functions, but cognitive functions, including social understanding, may also be impaired. Von Economo neurons (VENs) are part of the neuronal substrate of social understanding and these cells are histopathologically altered in ALS. We investigated whether activity in areas including VENs is associated with an i...

Objective The clinical manifestation of amyotrophic lateral sclerosis (ALS) is characterized by motor neuron degeneration, whereas frontotemporal dementia (FTD) patients show alterations of behavior and cognition. Both share repeat expansions in C9orf72 as the most prevalent genetic cause. Before disease-defining symptoms onset, structural and func...

Background: During the course of amyotrophic lateral sclerosis (ALS), patients and their families are faced with existential decisions concerning life-prolonging and -shortening measures. Correct anticipation of patient’s well-being and preferences is a prerequisite for patient-centered surrogate decision making. Methods: In Germany (N = 84), Polan...

Imaging studies showed that the structure of the corpus callosum (CC) is affected in amyotrophic lateral sclerosis (ALS). Some clinical studies also suggest that interhemispheric connectivity is altered, since mirror movements seem to occur in ALS. Finally, reduced interhemispheric inhibition (IHI), studied by transcranial magnetic stimulation (TMS...

Background: Spinal Muscular Atrophy (SMA) is a severe neurodegenerative disease, characterized by progressive muscle weakness and atrophy. The approval of the antisense oligonucleotide (ASO) nusinersen now provides an effective pharmacological approach with the potential to slow down or stop disease progression with a potentially major impact on pa...

Background C9orf72 hexanucleotide repeat expansions are associated with widespread cerebral alterations, including white matter alterations. However, there is lack of information on changes in commissure fibres. Diffusion tensor imaging (DTI) can identify amyotrophic lateral sclerosis (ALS)-associated patterns of regional brain alterations at the g...

Motor neuron diseases, such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), share several clinical similarities while differing substantially in etiology, disease onset and progression. Cognitive dysfunction, a clinically relevant non-motor feature in a substantial proportion of ALS patients, has been less frequently inves...

Background Studies provide inconclusive results on the question whether loss of mental wellbeing is actually associated with decline in physical function in amyotrophic lateral sclerosis (ALS). The purpose of this study was to determine predictors of mental wellbeing in ALS.Methods In total, n = 330 ALS patients were interviewed on parameters of me...

Background A mutation in C9orf72 constitute a cross-link between amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD). At clinical manifestation, both patient groups may present with either cognitive impairment of predominantly behaviour or language (in FTD) or motor dysfunctions (in ALS). Methods In total, 36 non-symptomatic mut...

Beatmungstherapie wird in der Neurologie außer bei intensivmedizinisch betreuten Patienten hauptsächlich bei progredienten neurodegenerativen und neuromuskulären Erkrankungen eingesetzt. Wird in der Intensivmedizin normalerweise passager beatmet, was einen negativen prognostischen Faktor darstellt, ist die Beatmung bei Patienten mit neurodegenerati...

Background A wide variety of metabolic changes, including an increased incidence of diabetes mellitus (DM) and dyslipidaemia, has been described in amyotrophic lateral sclerosis (ALS). The aim of this study was to investigate the associations of statin use and history of DM with onset of disease and survival in patients with ALS. Methods 501 patie...

PurposeThe aim of the study was to define specific substrates of pathological behaviour patterns by analysing cortical activity using functional magnetic resonance imaging (fMRI) during an emotional processing task.Methods In a sample of N = 11 adolescent patients with AN (16.36 years, SD ± 1.36) and N = 11 age-matched controls, we performed a func...

Background Diffusion tensor imaging (DTI) can identify amyotrophic lateral sclerosis (ALS)-associated patterns of brain alterations at the group level according to a neuropathological staging system. Objective The study was designed to investigate the in vivo staging in ALS patients with the C9orf72 expansion and potential differences to ALS patie...

There are a number of physical restrictions that develop in the course of amyotrophic lateral sclerosis (ALS). While loss of speech and motor control may be partially compensated by the support of assistive devices, swallowing difficulty and respiratory insufficiency require medical interventions (percutaneous endoscopic gastrostomy, noninvasive, a...

The attempt to quietly fixate at a small visual object is continuously interrupted by a variety of fixational eye movements comprising, among others, a continuum of saccadic intrusions (SI) which range in size from microsaccades with amplitudes ≤0.25° to larger refixation saccades of up to about 2°. The size and frequency of SI varies considerably...

Ethnic disparity of cerebral small vessel disease (CSVD) has been reported previously but understanding of its clinical-anatomical is sparse. Two cohorts of CSVD patients from Peking University First Hospital, China and University Hospital of Ulm, Germany were retrospectively collected between 2013 and 2017. Visual rating scales and semiautomatic c...

Objective This is an observational study on well-being and end-of-life preferences in patients with amyotrophic lateral sclerosis (ALS) in the locked-in state (LIS) in a Polish sample within the EU Joint Programme-Neurodegenerative Disease Research study NEEDSinALS (NEEDSinALS.com).Methods In this cross-sectional study, patients with ALS in LIS (n...

It is one of the primary goals of medical care to secure good quality of life (QoL) while prolonging survival. This is a major challenge in severe medical conditions with a prognosis such as amyotrophic lateral sclerosis (ALS). Further, the definition of QoL and the question whether survival in this severe condition is compatible with a good QoL is...

Objective: To investigate moral judgment competence in patients with the behavioral variant frontotemporal dementia (bvFTD) compared to amyotrophic lateral sclerosis (ALS) and controls. Methods: N = 12 bvFTD, N = 22 ALS patients and N = 19 neurological unimpaired controls were examined. In the 'Moral Competence Test' (MCT), participants had to e...

This study aimed to clarify whether differences between German and Chinese studies using the standardized Edinburgh Cognitive and Behavioural ALS Screen (ECAS), might be explained by differences in translated versions of ECAS, by patient demographic or clinical characteristics or by population-specific factors. Comparisons were performed on data fr...

Objective To determine the evolution and profile of cognitive and behavioural deficits in amyotrophic lateral sclerosis (ALS) and behavioural variant frontotemporal dementia (bvFTD) to disentangle the development of FTD in ALS and vice versa. Methods In a prospective design, cognitive and behavioural profiles of 762 patients with motor predominant...

Background: In many neurological conditions, there is a combination of decline in physical function and cognitive abilities. For far advanced stages of physical disability where speaking and hand motor abilities are severely impaired, there is a lack of standardized approach to screen for cognitive profile. Methods:N = 40 healthy subjects were incl...

Objective: Quantitative analysis of decision-making on therapeutic options in different sociocultural context in amyotrophic lateral sclerosis (ALS). Methods: ALS patients (n = 244) were consecutively recruited in Germany (n = 83), Poland (n = 83), and Sweden (n = 78) in a prospective cross-cultural study ( www.NEEDSinALS.com ). They were interv...

Cognitive deficits, especially in the domains of social cognition and executive function including verbal fluency, are common in amyotrophic lateral sclerosis (ALS) patients. There is yet sparse understanding of pathogenesis of the underlying, possibly adaptive, cortical patterns. To address this issue, 65 patients with ALS and 33 age-, gender- and...

In addition to motor neurone degeneration, up to 50% of amyotrophic lateral sclerosis (ALS) patients present with cognitive decline. Understanding the neurobiological changes underlying these cognitive deficits is critical, as cognitively impaired patients exhibit a shorter survival time from symptom onset. Given the pathogenic role of synapse loss...

Objective: The aim of this study is to explore phenotypical differences of amyotrophic lateral sclerosis (ALS) between two cohorts from Germany and China. Methods: Registry-based studies of ALS were conducted in South-West Germany from 2010 to 2014 and an ALS clinic in Beijing from 2013 to 2016, respectively. Demographic and clinical features of...

Background Healthcare legislation in European countries is similar in many respects. Most importantly, the framework of informed consent determines that physicians have the duty to provide detailed information about available therapeutic options and that patients have the right to refuse measures that contradict their personal values. However, when...

Objective Neuropathological studies in amyotrophic lateral sclerosis (ALS) have shown a dissemination in a regional sequence in four anatomically defined patterns. The aim of this retrospective study was to see whether longitudinal diffusion tensor imaging (DTI) data support the pathological findings. Methods The application of DTI analysis to fib...

Background The underlying pathological process in neurodegenerative diseases is associated with altered functional brain organization. Objective To study functional connectivity and its possible behavioral correlates in specific networks in patients with progressive supranuclear palsy (PSP). Methods Whole-brain based “resting-state” fMRI data fro...

Introduction Neuropathological studies in amyotrophic lateral sclerosis (ALS) have shown that ALS may disseminate in a regional sequence in four disease-related patterns (Braak et al., 2013). Recently, our group reported the diffusion tensor imaging (DTI)-based analysis of sequential spreading of disease in ALS (Kassubek et al., 2014; Müller et al....

We assessed language, attention, executive, and social cognition abilities in a sample of patients with Amyotrophic Lateral Sclerosis (ALS) by means of a recently developed cognitive battery based on oculomotor control with eye-tracking (ET) technology. Twenty-one ALS patients and 21 age- and education-matched healthy subjects underwent the ET-base...

Background: The topography of functional network changes in progressive supranuclear palsy can be mapped by intrinsic functional connectivity MRI. The objective of this study was to study functional connectivity and its clinical and behavioral correlates in dedicated networks comprising the cognition-related default mode and the motor and midbrain...

Objective: Reliable assessment of cognitive functions is a challenging task in amyotrophic lateral sclerosis (ALS) patients unable to speak and write. We therefore present an eye-tracking based neuropsychological screening tool based on the Edinburgh Cognitive and Behavioural ALS Screen (ECAS), a standard screening tool for cognitive deficits in A...

Despite the fatal outcome and progressive loss of physical functioning in amyotrophic lateral sclerosis (ALS), many patients maintain contentment in life. It has been shown that non-professionals tend to underestimate the well-being of patients with ALS, but professionals’ perspective is yet to be studied. In total, 105 neurologists with varying de...

The objective of this study is to determine the current distribution of clinical phenotypes and to estimate future trends of ALS incidence in Western societies. We report on a clinical-epidemiological registry with a capture–recapture rate of >80% and population-based case–control study in ALS patients in South Western Germany. 1163 incidents of AL...

Read the full paper here: http://rdcu.be/oukF Traditional cognitive assessment in neurological conditions involving physical disability is often prevented by the presence of verbal–motor impairment; to date, an extensive motor–verbal-free neuropsychological battery is not available for such purposes. We adapted a set of neuropsychological tests, as...

Background: Attitudes among patients and relatives toward the degree of acceptable disability and the importance of aphasia are critical in deciding on decompressive hemicraniectomy (DHC) in malignant middle cerebral artery infarction (MMI). However, most MMI patients are not able to communicate their will. Furthermore, attitudes of healthy indivi...

‘Resting-state’ fMRI allows investigation of alterations in functional brain organization that are associated with an underlying pathological process. We determine whether abnormal connectivity in amyotrophic lateral sclerosis (ALS) in a priori-defined intrinsic functional connectivity networks, according to a neuropathological staging scheme and i...

Introduction Amyotrophic lateral sclerosis (ALS) primarily impairs motor abilities but also affects cognition and emotional processing. We hypothesise that subjective ratings of emotional stimuli depicting social interactions and facial expressions is changed in ALS. It was found that recognition of negative emotions and ability to mentalize other’...

Questionnaire on social contacts in German. (DOCX)

Copyright permission for Fig 1. (PDF)

Questionnaire on social contacts in English. (DOCX)

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with pathological involvement of upper and lower motoneurons, subsequently leading to progressive loss of motor and speech abilities. In addition, cognitive functions are impaired in a subset of patients. To evaluate these potential deficits in severely physically impaired ALS pati...

The syndrome of pathological laughing and crying (PLC) is characterized by episodes of involuntary outbursts of emotional expression. Although this phenomenon has been referred to for over a century, a clear-cut clinical definition is still lacking, and underlying pathophysiological mechanisms are not well understood. In particular, it remains ill-...

Background Recordings of eye movements have demonstrated that oculomotor dysfunction in patients with amyotrophic lateral sclerosis (ALS) follows a two-staged pattern (Gorges et al., 2015) that is consistent with the model of sequential corticofugal axonal spread of pTDP-43 pathology (Brettschneider et al., 2013). Eye movement abnormalities in ALS...

There is a need for diagnostic, prognostic, and monitoring blood biomarkers for ALS. We aimed to analyse and compare proposed candidate markers for disease progression in the course of ALS. Blood samples were taken from 125 ALS patients, including nine patients with C9orf72 or SOD1 mutation, at regular intervals of six months. ALS patients were cha...

Objective: To investigate the use of P300-based Brain Computer Interface (BCI) technology for the administration of motor-verbal free cognitive tests in Amyotrophic Lateral Sclerosis (ALS). Methods: We recruited 15 ALS patients and 15 age- and education-matched healthy subjects. All participants underwent a BCI-based neuropsychological assessmen...

The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) has been developed to assess cognition and behaviour in patients with amyotrophic lateral sclerosis (ALS). Cognitive impairments of ALS-specific and ALS-non-specific functions can be determined using cut-off scores based on performance of healthy subjects. However, detailed analyses show tha...

Objective To see whether the sequential corticofugal spreading of pTDP-43 pathology in amyotrophic lateral sclerosis (ALS) (Brettschneider et al., Ann Neurol 2013) permit the categorization of eye movement disturbances in a corresponding oculomotor staging scheme. Methods Saccadic and smooth pursuit eye movements were video-oculographically recorde...