No abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes progressive autonomy loss and need for care. This does not only affect patients themselves, but also the patients’ informal caregivers (CGs) in their health, personal and professional lives. The big efforts of this multi-center study were not only to evaluate the caregivers’ burden and to identify its predictors, but it also should provide a specific understanding of the needs of ALS patients’ CGs and fill the gap of knowledge on their personal and work lives. Using standardized questionnaires, primary data from patients and their main informal CGs (n = 249) were collected. Patients’ functional status and disease severity were evaluated using the Barthel Index, the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and the King’s Stages for ALS. The caregivers’ burden was recorded by the Zarit Burden Interview (ZBI). Comorbid anxiety and depression of caregivers were assessed by the Hospital Anxiety and Depression Scale. Additionally, the EuroQol Five Dimension Five Level Scale evaluated their health-related quality of life. The caregivers’ burden was high (mean ZBI = 26/88, 0 = no burden, ≥24 = highly burdened) and correlated with patients’ functional status (rp = −0.555, p < 0.001, n = 242). It was influenced by the CGs’ own mental health issues due to caregiving (+11.36, 95% CI [6.84; 15.87], p < 0.001), patients’ wheelchair dependency (+9.30, 95% CI [5.94; 12.66], p < 0.001) and was interrelated with the CGs’ depression (rp = 0.627, p < 0.001, n = 234), anxiety (rp = 0.550, p < 0.001, n = 234), and poorer physical condition (rp = −0.362, p < 0.001, n = 237). Moreover, female CGs showed symptoms of anxiety more often, which also correlated with the patients’ impairment in daily routine (rs = −0.280, p < 0.001, n = 169). As increasing disease severity, along with decreasing autonomy, was the main predictor of caregiver burden and showed to create relevant (negative) implications on CGs’ lives, patient care and supportive therapies should address this issue. Moreover, in order to preserve the mental and physical health of the CGs, new concepts of care have to focus on both, on not only patients but also their CGs and gender-associated specific issues. As caregiving in ALS also significantly influences the socioeconomic status by restrictions in CGs’ work lives and income, and the main reported needs being lack of psychological support and a high bureaucracy, the situation of CGs needs more attention. Apart from their own multi-disciplinary medical and psychological care, more support in care and patient management issues is required.

The study of pathological laughter and crying (PLC) allows insights into the neural basis of laughter and crying, two hallmarks of human nature. PLC is defined by brief, intense and frequent episodes of uncontrollable laughter or crying provoked by trivial stimuli. It occurs secondary to CNS disorders such as stroke, tumours or neurodegenerative diseases. Based on case studies reporting various lesions locations, PLC has been conceptualized as dysfunction in a cortico-limbic-subcortico-thalamo-ponto-cerebellar network. To test whether the heterogeneous lesion locations are indeed linked in a common network, we applied ‘lesion network-symptom-mapping’ (LNSM) to 70 focal lesions identified in a systematic literature search for case reports of PLC. In LNSM normative connectome data (resting state functional MRI, n = 100) is used to identify the brain regions which are likely affected by diaschisis based on the lesion locations. With LNSM we were able to identify a common network specific for PLC when compared with a control cohort (n = 270). This bilateral network is characterized by positive connectivity to the cingulate and temporomesial cortices, striatum, hypothalamus, mesencephalon and pons and negative connectivity to the primary motor and sensory cortices. In the most influential pathophysiological model of PLC, a center for the control and coordination of facial expressions, respiration and vocalization in the periaqueductal grey is assumed which is controlled via two pathways: an emotional system that exerts excitatory control of the periaqueductal grey descending from the temporal and frontal lobes, basal ganglia and hypothalamus and a volitional system descending from the lateral premotor cortices which can suppress laughter or crying. To test whether the positive and negative PLC subnetworks identified in our analyses can indeed be related to an emotional system and a volitional system, we identified lesions causing emotional (n = 15) or volitional facial paresis (n = 46) in a second literature search. Patients with emotional facial paresis show preserved volitional movements but cannot trigger emotional movements in the affected hemiface, while the reverse is true for volitional facial paresis. Importantly, these lesions map differentially onto the PLC subnetworks: the ‘positive PLC subnetwork’ is part of the emotional system and the ‘negative PLC subnetwork’ overlaps with the volitional system for the control of facial movements. Based on this network analysis we propose a two-hit model of PLC: a combination of direct lesion and indirect diaschisis effects cause PLC through the loss of inhibitory cortical control of a dysfunctional emotional system.

Background and purpose Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with predominant progressive degeneration of motor neurons and motor deficits, but non‐motor symptoms (NMS) such as cognitive and behavioural deficits are frequent and underestimated in current diagnostic pathways. Autonomic dysfunction has occasionally been described, although its frequency and relevance are unclear. The aim of this study was to investigate the role of the autonomic nervous system in ALS using a multimodal approach. Methods Thirty‐seven ALS patients and 40 healthy sex‐ and age‐matched controls were included. NMS were studied with the NMS assessment scale for Parkinson's disease and an autonomic subscale was calculated. Cardioautonomic innervation at rest and whilst standing was assessed by different parameters of heart rate variability. Morphological changes (cross‐sectional area) of the vagus and median nerves for control were measured with high‐resolution ultrasound. Results Non‐motor symptoms in general were more frequent in ALS patients and correlated inversely with the ALS Functional Rating Scale whereas the autonomic subscore of the NMS assessment scale for Parkinson's disease did not differ between the two groups and was not related to functional impairment. Cardioautonomic assessment solely revealed an increased heart rate at rest in ALS patients, whereas the other heart rate variability parameters did not differ from controls. Structural sonographic investigation of the vagus and median nerves was similar in both groups. Conclusions Using a multimodal approach evidence was found for a rather mild cardio‐sympathetic overactivity in ALS patients. Overall, autonomic dysfunction seems to be subtle and is not related to the functional state of ALS patients.