Gastrostomy and mechanical ventilation in amyotrophic lateral sclerosis: how best to support the decision-making process?

The unfavourable outcome of amyotrophic lateral sclerosis (ALS) confronts patients with challenging decisions regarding life-sustaining measures. The decision-making process is usually triggered by medical consultations and patient-dependent factors. This may largely depend on the physician's depth of knowledge and professional experience. This paper presents an overview of the life-sustaining methods used in ALS and their effects on disease progression, survival and quality of life of patients and their caregivers. It is intended to aid physicians in their discussions with patients. We interrogate all the positive and negative facets of life-sustaining measures that may allow for optimisation of the decision-making process and care provision.

Positron emission tomography neuroimaging in neurodegenerative diseases: Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.

Neurodegenerative diseases are a growing problem of ageing societies. Their insidious onset, and the lack of reliable biomarkers, result in significant diagnosis delays. This article summarises the results of studies on the use of positron emission tomography (PET) in the diagnosis of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. It focuses on clinical-pathogenetic aspects of individual diseases, as well as disease-specific patterns relevant in differential diagnosis and in assessing the risk of disease development and prognosis.

One third of physicians discuss exit strategies with patients with amyotrophic lateral sclerosis: Results from nationwide surveys among German and Polish neurologists.

OBJECTIVE: This paper examines neurologists' approaches to exit strategies (ESs), such as euthanasia and physician-assisted suicide, in patients with amyotrophic lateral sclerosis (PALS) in two European countries. METHODS: In a nationwide anonymous survey, we collected responses from 237 Polish and 228 German neurologists, focusing on their practices and beliefs about ESs, as well as their viewpoints on life-sustaining measures (LSMs) (percutaneous endoscopic gastrostomy, non-invasive, and invasive ventilation). To analyze the data, we employed statistical methods, including Mann-Whitney U, Kruskal-Wallis, chi-square tests, Spearman's rank correlation, and multiple regression analysis. RESULTS: One third of the neurologists initiated the discussion about ESs with PALS. Half were ready to have this conversation upon patient's request. Age, gender, religiousness, and nationality were closely associated with this approach. One in 9 neurologists received a request to terminate an LSM, whereas 1 in 10 to implement an ES. German neurologists and palliative care trainees acquired both demands more commonly. Neurologists quoted a low quality of life, decreased mood, and being a burden to the family/closest ones as primary reasons for a wish to hasten death among PALS. Although the majority expressed a willingness to terminate an LSM at a request of the patient, most opposed the legalization of euthanasia. Younger and less religious individuals were more likely to favor accepting euthanasia. CONCLUSION: Neurologists vary significantly in their approaches to terminal care. Complex relationships exist among personal indices, shared beliefs, and current practices.

Physical activity in patients with amyotrophic lateral sclerosis: Prevalence, patients' perspectives and relation to the motor performance.

BACKGROUND: There are no recommendations for physical activity in amyotrophic lateral sclerosis (ALS) patients. OBJECTIVE: (i) To describe the prevalence and pattern of physical activity (PA) in ALS patients; (ii) to explore patients' attitude towards PA; and (iii) to investigate the relationship between PA at home environment and the rate of functional decline. METHODS: 96 ALS patients were followed for 6 months at 3-month intervals and assessed by site of disease onset, disease duration, diagnosis delay, functional status, muscle strength, fatigue and prevalence of PA. RESULTS: Over 70% of patients performed regular exercise and reported a positive effect of PA on functional status and mood. Regularly exercising individuals showed a higher ALSFRS-R bulbar score (11.0 vs 9.0, p = 0.011) and a lower decline of respiratory sub-score of ALSFRS-R compared to non-regularly exercising patients (0 vs 1.0, p = 0.026). Bulbar onset was a negative prognostic factor for regular exercise (odds ratio [OR]: 5.2, p = 0.004). CONCLUSION: The majority of ALS patients perform regular PA and find it positively influence their motor performance and mood. Bulbar disease onset, but not functional status, is a negative prognostic factor for regular exercise in ALS patients. Regular mild PA may result in a slower deterioration of functional status, especially the respiratory function.

Well-being on supportive techniques in amyotrophic lateral sclerosis: from neurologists' perspective.

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 anonymous questionnaires addressing the clinical approach and personal attitude towards the use of PEG, NIV and IV in ALS patients completed by 465 neurologists: 228 from Germany and 237 from Poland. RESULTS: The German and Polish neurologists estimated the quality of life in ALS patients using PEG and NIV as neutral, whilst low in individuals using IV. A regression model revealed an independent influence of palliative care training (PCT) and age on that attitude in the German group. Higher values of estimated patients' depressiveness on PEG, NIV and IV were found amongst the Polish neurologists. Marital status, experience in ALS and being a parent independently influenced the perception of patients' depressiveness in the German, whilst marital status, age and PCT were factors in the Polish group. Amongst German neurologists, a higher perception of patients' depressiveness in individuals using PEG, NIV and IV was linked to the later timing of the MIs discussion. In the Polish group, it was a lower estimation of QoL in patients using PEG. CONCLUSION: Neurologists' perception of ALS patients' well-being on MIs reflects their demographic status, professional experience and potentially their cultural background. This perception plays an important role in the timing of MIs discussion, possibly influencing the decision-making process.

Caregivers' divergent perspectives on patients' well-being and attitudes towards hastened death in Germany, Poland and Sweden.

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), Poland (N = 77) and Sweden (N = 73) patient-caregiver dyads were interviewed. Standardized questionnaires on well-being (ADI-12 for depressiveness; ACSA for global quality of life) and wish for hastened death (SAHD) were used in ALS patients. Additionally, caregivers were asked to fill out the same questionnaires by anticipating patients' perspective (surrogate perspective). Results: Caregivers significantly underestimated patients' well-being in Germany and Poland. For Swedish caregivers, there were just as many who underestimated and overestimated well-being. The same was true for wish for hastened death in all three countries. For Swedish and Polish patients, caregivers' estimation of well-being was not even associated with patients' responses and the same was true for estimation of wish for hastened death in all three countries. Older caregivers and those with the most frequent encounter with the patient were the closest in their rating of well-being and wish for hastened death to the patients' actual state, while caregivers with chronic disease him/herself were more likely to underestimate patient's well-being. Discussion: Despite distinct cultural differences, there was a clear discrepancy between patients' and caregivers' perspective on patients' well-being and preferences towards life in all three countries. This possible bias in caregivers' judgment needs to be taken into account in surrogate decision making.

The relationship between aquaporin-4 antibody status and visual tract integrity in neuromyelitis optica spectrum disorders: A visual evoked potential study.

BACKGROUND: Optic neuritis (ON) is one of the hallmark symptomatic features of neuromyelitis optica spectrum disorders (NMOSD). The majority of patients with NMOSD present highly specific autoantibodies against aquaporin-4 (AQP4). A number of studies have reported poor visual acuity outcomes in individuals with AQP4 seropositive NMOSD, but no such relationship has been found with regard to visual evoked potentials (VEP) parameters such as the amplitude and latency of the P100 component. In this paper, we aimed (i) to describe VEP responses in patients with NMOSD; (ii) to analyze those results based on a scoring system; and (iii) to investigate the association between the VEPs and AQP4 antibody status. METHODS: We retrospectively analysed the VEP responses of 40 patients with a diagnosis of NMOSD (according to the 2015 IPND criteria), including 16 with AQP4-postive status (AQP4[+]) and 24 with AQP4-negative status (AQP4[-]). In the first step, we measured the P100 peak latency and P100-N2 peak-to-peak amplitude in each patient. In the second, we converted these measures to the VEP score (0-10) using the scoring proposed by Jung et al. (2008). All recordings were performed using the same VEP device and testing protocol. RESULTS: Abnormal VEPs were recorded in 25 of 40 patients (62.6%). Of these, 17 (42.5%) had prolonged P100 latency, and 8 (20%) had no response detected in at least one eye. The patients with ON as the initial relapse symptom had significantly higher median VEP scores than those who experienced the longitudinally extensive transverse myelitis (LETM) at the disease onset (7.0 [in-terquar-tile range (IQR), 2.0-8.0] vs. 0.0 [IQR, 0.0-4.0], p<0.001). A lack of VEP response in at least one eye was detected more frequently in the AQP4[+] group than the AQP4[-] group (7/16 vs. 1/24, p<0.005). Logistic regression model controlling for age, gender, disease duration, and the type of relapse at onset showed an independent impact of AQP4[+] status (OR=35.45, p = 0.018) on the higher rate of absent VEP responses. In the entire group of patients (n = 40), those with AQP4[+] showed a small tendency towards a higher median VEP score (4.0 [IQR, 0.0-7.8] vs. 1.0 [IQR, 0.0-4.0], p = 0.304). Among individuals with abnormal responses (n = 25), the patients with AQP4[+] had significantly higher median VEP scores (7.0 [IQR, 4.0-8.5] vs. 3.0 [IQR, 1.0-7.0], p = 0.034) and more common bilateral involvement of the optic tracts (80% vs. 40%, p = 0.048) than those who were seronegative for anti-AQP4 antibody. A median regression analysis model controlling for age, gender, disease duration, type of onset, and number of relapses in last 12 months showed an independent association between the AQP4-positive status and a higher VEP score in patients with NMOSD (t = 2.882, df=2, p = 0.007). CONCLUSION: VEP study remains a useful tool in the assessment of NMOSD patients. Due to the high prevalence of absent VEPs in NMOSD patients, the scoring system appears to be more applicable for the precise analysis of VEP recordings. There is a positive association between the AQP-positive serostatus and the poorer outcome in VEP responses, especially in patients with severe impairment of the optic nerve(s).

Healthcare provision in amyotrophic lateral sclerosis: procedures, queries and pitfalls in Germany and Poland.

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, and invasive ventilation). Based on the data collected within the NEEDSinALS study, we found major differences in personal satisfaction with the financing, healthcare provision, medical infrastructure, and regulations of German and Polish ALS patients, despite minor differences in economic burden caused by the disease. In order to explain this phenomenon, we thoroughly reviewed the legal basis, structure and organization of the healthcare systems in Germany and Poland to determine the range of obstacles in the everyday lives of patients and their caregivers that are attempting to attain an assistive device or care after the start of medical interventions.

Search for viral agents in cerebrospinal fluid in patients with multiple sclerosis using real-time PCR and metagenomics.

Multiple sclerosis (MS) is a chronic, immune-mediated demyelinating disease of the central nervous system of unclear etiology, but there is some evidence that viral infections could be responsible for triggering autoimmune mechanisms against myelin. We searched for viral RNA and DNA in cerebrospinal fluid (CSF) of 34 MS patients and 13 controls using RT-PCR/PCR against common neurotropic viruses. In addition, shotgun DNA- and RNA-based metagenomics were done in 13 MS patients and 4 controls. Specific quantitative real-time RT-PCR/PCR testing revealed the presence of viral nucleic acid in seven (20.59%) MS patients and in one (7.69%) control patient. In MS patients the most frequently detected was human herpesvirus type 6 (HHV-6; 3 cases; 8.82%); followed by Epstein-Barr virus (EBV; 2 cases; 5.88%), varicella zoster virus (VZV; 1 case; 2.94%) and Enterovirus (EV; 1 case; 2.94%). The single identified virus among controls was EBV (7.69%). DNA and RNA metagenomic assays did not identify any known eukaryotic viruses even though three of the analyzed samples were low-level positive by specific quantitative real-time PCR. In conclusion, we detected the presence of Herpesviridae and occasionally Enteroviridae in CSF from patients with MS but their prevalence was not significantly higher than among controls. Metagenomic analysis seems to be less sensitive than real-time RT-PCR/PCR and it did not detect any potential viral pathogens.

Emotional Lability at Disease Onset Is an Independent Prognostic Factor of Faster Disease Progression in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fast progressing neurodegenerative disease leading to quadriplegia, anarthria and respiratory insufficiency. A large variety of phenotypes and disability progression requires individually tailored management. Identification of predictors of poor prognosis may not only improve management, but also allow for more precise patients' stratification for clinical trials or research studies. The aim of the study was to investigate the influence of emotional lability present at disease onset on ALS progression by exploring its direct impact on the decay of the ALS Functional Rating Scale-Revised (ALSFRS-R). The study was performed in a group of 1145 patients from Germany, Poland, Portugal and Turkey between 2014 and 2018. The analysis showed that the presence of emotional lability at ALS onset was linked to a faster decline of ALSFRS-R (0.70 vs 0.50, p<0.0001), in case of either bulbar (0.80 vs 0.65, p<0.05) or limb disease onset (0.59 vs 0.46, p <0.01). It was most prominent in the bulbar subscore of ALSFRS-R. A multiple regression analysis showed a direct influence of emotional lability at ALS onset on disease progression, regardless of age, gender, site of onset, weight loss, cognitive impairment and diagnosis delay (ß=0.071; p=0.019). It can therefore be concluded that the presence of emotional lability at the disease onset is an independent factor of faster disease progression in ALS.