Disease progression but not physical state per se determines mental wellbeing in ALS.

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 mental wellbeing to evaluate the patients' capacity of psychosocial adaptation. These parameters were global and subjective quality of life (QoL), and depressiveness. A subsample of n = 82 ALS patients were interviewed again within approximately a year (mean 14.34 ± 5.53 months). RESULTS: Both global and subjective QoL were stable, whereas depressiveness increased within the course of 1 year after diagnosis. Physical function decline was associated with mental wellbeing. Progression of physical disabilities and symptom duration were significant predictors of wellbeing in the sense that fast progression and short time since symptom onset (both indicating short time to adapt) were associated with low wellbeing. CONCLUSIONS: There is evidence for subsamples in ALS with regard to mental wellbeing, which are mainly determined by clinical parameters. Those subjects being reported in the literature to present with high mental wellbeing are often long survivors. High progression rate and low physical function when attending the clinic for the first time should be red flags and need special attention in clinical counseling.

Story of the ALS-FTD continuum retold: rather two distinct entities.

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 ALS (flail arm/leg syndrome, primary lateral sclerosis, pseudobulbar palsy, ALS) and behavioural predominant FTD (bvFTD, ALS-FTD) were determined and caregivers of patients with ALS were asked on the evolution of behavioural symptoms. Data were compared with 49 healthy controls. Cognition was measured with the Edinburgh Cognitive and Behavioral ALS Screen. RESULTS: Evolution and features of cognitive profile of patients with motor predominant ALS were distinctly different from patients with behavioural FTD with regard to number and degree of affected cognitive domains. Also, in ALS mostly minus symptoms evolved after physical symptom onset whereas in ALS-FTD plus and minus symptoms were reported with an onset before physical degradation. CONCLUSION: Evolution of cognitive and behavioural profile in patients with motor predominant ALS is distinctly different from those psychocognitive findings in patients with behavioural variant dementia. This may support the hypothesis that (possibly genetic) triggers decide in the preclinical phase on either motor or psychocognitive phenotypes.

Functional reorganization during cognitive function tasks in patients with amyotrophic lateral sclerosis.

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 education-matched healthy controls were tested on cognitive and behavioral deficits with the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Using functional magnetic resonance imaging (fMRI), cortical activity during social cognition and executive function tasks (theory of mind, verbal fluency, alternation) adapted from the ECAS was determined in a 3 Tesla scanner. Compared to healthy controls, ALS patients performed worse in the ECAS overall (p < 0.001) and in all of its subdomains (p < 0.02), except memory. Imaging revealed altered cortical activation during all tasks, with patients consistently showing a hyperactivation in relevant brain areas compared to healthy controls. Additionally, cognitively high performing ALS patients consistently exhibited more activation in frontal brain areas than low performing patients and behaviorally unimpaired patients presented with more neuronal activity in orbitofrontal areas than behaviorally impaired patients. In conclusion, hyperactivation in fMRI cognitive tasks seems to represent an early adaptive process to overcome neuronal cell loss in relevant brain areas. The hereby presented cortical pattern change might suggest that, once this loss passes a critical threshold and no cortical buffering is possible, clinical representation of cognitive and behavioral impairment evolves. Future studies might shed light on the pattern of cortical pattern change in the course of ALS.

A first approach to a neuropsychological screening tool using eye-tracking for bedside cognitive testing based on the Edinburgh Cognitive and Behavioural ALS Screen.

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 ALS. METHODS: In total, 46 ALS patients and 50 healthy controls matched for age, gender and education were tested with an oculomotor based and a standard paper-and-pencil version of the ECAS. RESULTS: Significant correlation between both versions was observed for ALS patients and healthy controls in the ECAS total score and in all of its ALS-specific domains (all r > 0.3; all p < 0.05). The eye-tracking version of the ECAS reliably distinguished between ALS patients and healthy controls in the ECAS total score (p < 0.05). Also, cognitively impaired and non-impaired patients could be reliably distinguished with a specificity of 95%. CONCLUSION: This study provides first evidence that the eye-tracking based ECAS version is a promising approach for assessing cognitive deficits in ALS patients who are unable to speak or write.

Experience matters: neurologists' perspectives on ALS patients' well-being.

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 degrees of experience with ALS were included in an anonymous survey. They were asked to estimate the quality of life and depressiveness of ALS patients with artificial ventilation and nutrition. Physicians' estimations were compared with previously reported subjective ratings of ALS patients with life-prolonging measures. Neurologists with significant experience on ALS and palliative care were able to accurately estimate depressiveness and quality of life of ALS patients with life-prolonging measures. Less experienced neurologists' estimation differed more from patients' reports. Of all life-prolonging measures neurologists regarded invasive ventilation as the measure associated with lowest quality of life and highest depressiveness of the patients. Experienced neurologists as well as neurologists with experience in palliative care are able to better empathize with patients with a fatal illness such as ALS and support important decision processes.

Eye-Tracking Control to Assess Cognitive Functions in Patients with Amyotrophic Lateral Sclerosis.

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 patients, eye-tracking is a promising means to conduct cognitive tests. The present article focuses on how eye movements, an indirect means of communication for physically disabled patients, can be utilized to allow for detailed neuropsychological assessment. The requirements, in terms of oculomotor parameters that have to be met for sufficient eye-tracking in ALS patients are presented. The properties of stimuli, including type of neuropsychological tests and style of presentation, best suited to successfully assess cognitive functioning, are also described. Furthermore, recommendations regarding procedural requirements are provided. Overall, this methodology provides a reliable, easy to administer and fast approach for assessing cognitive deficits in patients who are unable to speak or write such as patients with severe ALS. The only confounding factor might be deficits in voluntary eye movement control in a subset of ALS patients.

Perception of Emotional Facial Expressions in Amyotrophic Lateral Sclerosis (ALS) at Behavioural and Brain Metabolic Level.

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's intentions is reduced. METHODS: Processing of emotions in faces was investigated. A behavioural test of Ekman faces expressing six basic emotions was presented to 30 ALS patients and 29 age-, gender and education matched healthy controls. Additionally, a subgroup of 15 ALS patients that were able to lie supine in the scanner and 14 matched healthy controls viewed the Ekman faces during functional magnetic resonance imaging (fMRI). Affective state and a number of daily social contacts were measured. RESULTS: ALS patients recognized disgust and fear less accurately than healthy controls. In fMRI, reduced brain activity was seen in areas involved in processing of negative emotions replicating our previous results. During processing of sad faces, increased brain activity was seen in areas associated with social emotions in right inferior frontal gyrus and reduced activity in hippocampus bilaterally. No differences in brain activity were seen for any of the other emotional expressions. Inferior frontal gyrus activity for sad faces was associated with increased amount of social contacts of ALS patients. CONCLUSION: ALS patients showed decreased brain and behavioural responses in processing of disgust and fear and an altered brain response pattern for sadness. The negative consequences of neurodegenerative processes in the course of ALS might be counteracted by positive emotional activity and positive social interactions.

Eye-tracking controlled cognitive function tests in patients with amyotrophic lateral sclerosis: a controlled proof-of-principle study.

Amyotrophic lateral sclerosis (ALS) primarily affects motor and speech abilities. In addition, cognitive functions are impaired in a subset of patients. There is a need to establish an eye movement-based method of neuropsychological assessment suitable for severely physically impaired patients with ALS. Forty-eight ALS patients and thirty-two healthy controls matched for age, sex and education performed a hand and speech motor-free version of the Raven's coloured progressive matrices (CPM) and the D2-test which had been especially adapted for eye-tracking control. Data were compared to a classical motor-dependent paper-pencil version. The association of parameters of the eye-tracking and the paper-pencil version of the tests and the differences between and within groups were studied. Subjects presented similar results in the eye-tracking and the corresponding paper-pencil versions of the CPM and D2-test: a correlation between performance accuracy for the CPM was observed for ALS patients (p < 0.001) and controls (p < 0.001) and in the D2-test for controls (p = 0.048), whereas this correlation did not reach statistical significance for ALS patients (p = 0.096). ALS patients performed worse in the CPM than controls in the eye-tracking (p = 0.053) and the paper-pencil version (p = 0.042). Most importantly, eye-tracking versions of the CPM (p < 0.001) and the D2-test (p = 0.024) reliably distinguished between more and less cognitively impaired patients. Eye-tracking-based neuropsychological testing is a promising approach for assessing cognitive deficits in patients who are unable to speak or write such as patients with severe ALS.