Abstract Objective To determine whether serum creatine kinase activity (CK) and serum creatinine concentration (Crn) are prognostic and predictive biomarkers for disease severity, disease progression, and nusinersen treatment effects in adult patients with 5q‐associated spinal muscular atrophy (SMA). Methods Within this retrospective, multicenter observational study in 206 adult patients with SMA, we determined clinical subtypes (SMA types, ambulatory ability) and repeatedly measured CK and Crn and examined disease severity scores (Hammersmith Functional Motor Scale Expanded, Revised Upper Limb Module, and revised Amyotrophic Lateral Sclerosis Functional Rating Scale). Patients were followed under nusinersen treatment for 18 months. Results CK and Crn differed between clinical subtypes and correlated strongly with disease severity scores (e.g., for Hammersmith Functional Motor Scale Expanded: (CK) ρ = 0.786/ (Crn) ρ = 0.558). During the 18 months of nusinersen treatment, CK decreased (∆CK = −17.56%, p < 0.0001), whereas Crn slightly increased (∆Crn = +4.75%, p < 0.05). Interpretation Serum creatine kinase activity and serum creatinine concentration reflect disease severity of spinal muscular atrophy and are promising biomarkers to assess patients with spinal muscular atrophy during disease course and to predict treatment response. The decrease of creatine kinase activity, combined with the tendency of creatinine concentration to increase during nusinersen treatment, suggests reduced muscle mass wasting with improved muscle energy metabolism.
The finding of a good subjective quality of life (QoL) by Kuzma-Kozakiewicz et al.1 in patients with ALS in locked-in state (LIS) confirms our previous results.2 Although we agree with the authors and editorial3 that it is now necessary to conduct longitudinal studies starting at earlier disease stages, we would even set their starting points far before patients decide over mechanical ventilation to understand how this decision is influenced by internal states such as subjective QoL in interaction with external conditions. However, we mainly stress the need to gain more distinctive insights into the psychologic adaptation process underlying such outcomes in future work, taking patients but also their next of kin (NOK) into account. In this regard, what have been the SEIQol domains noted as important by patients and their NOK and how was the NOK's own QoL, considering that NOK often do not adapt properly?2 Beyond the selection bias of such studies, it is time to look deeper into social network changes,4 socioeconomic/religious factors5—but also patient's secondary morbid gain—and the question to what extent it occurs at the expense of their beloved ones. Finally, how significant are such results concerning end-of-life decisions and presumed patients' will beyond ALS?
Abstract Amyotrophic lateral sclerosis (ALS) can result into an incomplete locked in state (iLIS), in which communication depends on eye tracking computer devices. Oculomotor function impairments in ALS have been reported, but there is little research, particularly with respect to patients in iLIS. In the present study, we compared reflexive and executive oculomotor function by means of an eye tracking test battery between three groups: advanced ALS patients in iLIS (n = 22), patients in early to middle ALS stages (n = 44) and healthy subjects (n = 32). Patients with ALS showed significant deteriorations in oculomotor functions, with stronger impairments in iLIS. More specifically, ALS patients produced visually guided prosaccades with longer latencies and more frequent hypometria compared to healthy subjects. Longest latencies were obtained in iLIS patients, with a stronger prolongation for vertical than for horizontal prosaccades. ALS patients made more antisaccade errors and generated antisaccades with longer latencies. Smooth pursuit was also impaired in ALS. In the earlier ALS stages, bulbar onset patients presented stronger antisaccade and smooth pursuit deficits than spinal onset patients. Our findings reveal a relevant deterioration of important oculomotor functions in ALS, which increases in iLIS. It includes impairments of reflexive eye movements to loss of executive inhibitory control, indicating a progressing pathological involvement of prefrontal, midbrain and brainstem areas. The assessment of oculomotor functions may therefore provide clinically relevant bio- and progression marker, particularly in advanced ALS.
Multidimensional socio-medical care with an early integration of palliative principles is strongly recommended in amyotrophic lateral sclerosis (ALS), but provided inconsistently. We conducted telephone interviews with 49 former caregivers of deceased ALS patients to examine their experience of care in the terminal phase including caregiver burden. Patients who received specialized palliative care (45% of patients) were more likely to die at home (p = 0.004) and without burdening symptoms (p = 0.021). The majority of caregivers (86%) reported deficits in socio-medical care. Most frequently mentioned were problems receiving medical aids (45%) and a lack of caregiver support (35%). A higher level of deficits experienced by caregivers was associated with negative health outcomes on the side of the caregivers (reported by 57% of them; p = 0.002) and stronger caregiver burden (p = 0.004). To provide good quality of dying to patients and reduce the burden on caregivers, multidimensional-including palliative-care in ALS urgently needs to be strengthened in the healthcare structures.
Abstract Introduction Amyotrophic lateral sclerosis (ALS) is an inevitably fatal condition that leads to a progressive loss of physical functioning, which results in a high psychosocial burden and organizational challenges related to medical care. Multidimensional and multiprofessional care is advised to meet the complex needs of patients and their families. Many healthcare systems, including Germany, may not be able to meet these needs because non-medical services such as psychological support or social counselling are not regularly included in the care of patients with ALS (pwALS). Specialised neuropalliative care is not routinely implemented nor widely available. Caregivers of pwALS are also highly burdened, but there is still a lack of support services for them. Methods This project aims to assess the perceptions and satisfaction with ALS care in Germany in pwALS and their caregivers. This will be achieved by means of a cross-sectional, multicentre survey. The examination will assess, to which extend the patients’ needs in the six domains of physical, psychological, social, spiritual, practical and informational are being met by current care structures. This assessment will be linked to mental well-being, subjective quality of life, attitudes toward life-sustaining measures and physician-assisted suicide, and caregiver burden. The study aims to recruit 500 participants from nationwide ALS centres in order to draw comprehensive conclusions for Germany. A total of 29 centres, mostly acquired via the clinical and scientific German Network for Motor Neuron Diseases (MND-NET), will take part in the project, 25 of which have already started recruitment. Perspective It is intended to provide data-based starting points on how current practice of care in Germany is perceived pwALS and their caregivers and how it can be improved according to their needs. Planning and initiation of the study has been completed. Trial registration The study is registered at ClinicalTrails.gov; NCT06418646
Abstract For both patients with amyotrophic lateral sclerosis (ALS) and their next of kin (NOK), the maintenance of quality of life (QoL) and mental health is particularly important. First studies suggest significant discrepancies between QoL reports by patients and NOK, but little is known for advanced ALS stages. To address this issue, we screened 52 ALS patients in incomplete locked-in state (iLIS). Final results were obtained for 15 couples of iLIS patients and NOK. We assessed patients’ and NOK’s subjective QoL, depression and anxiety and NOK’s caregiver burden. Gaze controlled questionnaires allowed direct assessment of patients. Patients and NOK self-reported comparable, mostly moderate to high levels of QoL. Of note, NOK indicated stronger anxiety symptoms. Higher anxiety levels in NOK were associated with stronger caregiver burden and reduced QoL. No significant misjudgment of patient’s QoL by the NOK was evident, while patients overestimated NOK’s global QoL. However, NOK with severe caregiver burden and depression symptoms gave poorer estimations of patients’ QoL. This relationship is relevant, considering NOK’s impact on life critical treatment decisions. While the daily time NOK and patient spend together was positively correlated with NOK’s QoL and mental health, this was not reversely found for the patients. Our results suggest that NOK adapt less successfully to the disease and concomitant experience of loss and point to an urgent need for specialized psychosocial support. The findings emphasize the importance of direct psychological wellbeing assessment of both patients and NOK in clinical practice, enabled by eye-tracking technology for patients in iLIS.
Cognitive function is tested through speech- or writing-based neuropsychological instruments. The application and validity of those tests is impeded for patients with diseases that affect speech and hand motor skills. We therefore developed a "motor-free" gaze-controlled version of the Trail Making Test (TMT), including a calibration task to assess gaze accuracy, for completion by means of an eye-tracking computer system (ETCS). This electronic TMT version (eTMT) was evaluated for two paradigmatic "motor-neurodegenerative" diseases, Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). We screened 146 subjects, of whom 44 were excluded, e.g., because of vision deficits. Patients were dichotomized into subgroups with less (ALS-, PD-) or severe motor affection (ALS+, PD+). All 66 patients and all 36 healthy controls (HC) completed the eTMT. Patients with sufficient hand motor control (ALS-, PD-, PD+) and all HC additionally completed the original paper-pencil-based version of the TMT. Sufficient and comparable gaze fixation accuracy across all groups and the correlations of the eTMT results with the TMT results supported the reliability and validity of the eTMT. PD+ patients made significantly more errors than HC in the eTMT-B. We hereby proved the good applicability of a motor-free cognitive test. Error rates could be a particularly sensitive marker of executive dysfunction.
