Palliative care and circumstances of dying in German ALS patients using non-invasive ventilation.

Non-invasive ventilation (NIV) is known to improve quality of life and to prolong survival in amyotrophic lateral sclerosis (ALS) patients. However, little is known about the circumstances of dying in ventilated ALS patients. In the light of the debate on legalizing euthanasia it is important to provide empirical data about the process of dying in these patients. In a structured interview, 29 family caregivers of deceased ALS patients were asked about their own and the patient's attitude toward physician-assisted suicide (PAS) and euthanasia, circumstances of dying, and the use of palliative medication. Quantitative and qualitative content analysis was performed on the data. Non-recurring suicidal thoughts were reported by five patients. Three patients and seven relatives had thought about PAS. Seventeen caregivers described the patients' death as "peaceful", while choking was reported in six bulbar patients. In final stages of dying, the general practitioner (GP) was involved in the treatment of 10 patients, with palliative medication including sedatives and opiates being administered in eight cases. In conclusion, in contrast to the Netherlands, where 20% of terminal ALS patients die from PAS or euthanasia, only a small minority of our patients seems to have thought about PAS. The legal situation in Germany (where euthanasia is illegal), a bias due to the selection of NIV patients as well as a high percentage of religious patients and those with good levels of social support from family and friends, might account for this. Most of our patients died peacefully at home from carbon dioxide narcosis, but choking was described in some bulbar patients. Thus, palliative care, especially the use of opiates, anxiolytics and sedatives should be optimized, and the involvement of GP should be strongly encouraged, especially in bulbar patients.

Cortical plasticity in amyotrophic lateral sclerosis: motor imagery and function.

BACKGROUND: Cortical networks underlying motor imagery are functionally close to motor performance networks and can be activated by patients with severe motor disabilities. OBJECTIVE: The aim of the study was to examine the longitudinal effect of progressive motoneuron degeneration on cortical representation of motor imagery and function in amyotrophic lateral sclerosis. METHODS: The authors studied 14 amyotrophic lateral sclerosis patients and 15 healthy controls and a subgroup of 11 patients and 14 controls after 6 months with a grip force paradigm comprising imagery and execution tasks using functional magnetic resonance imaging. RESULTS: Motor imagery activated similar neural networks as motor execution in amyotrophic lateral sclerosis patients and healthy subjects in the primary motor (BA 4), premotor, and supplementary motor (BA 6) cortex. Amyotrophic lateral sclerosis patients presented a stronger response within premotor and primary motor areas for imagery and execution compared to controls. After 6 months, these differences persisted with additional activity in the precentral gyrus in patients as well as in a frontoparietal network for motor imagery, in which activity increased with impairment. CONCLUSION: The findings suggest an ongoing compensatory process within the higher order motor-processing system of amyotrophic lateral sclerosis patients, probably to overcome loss of function in primary motor and motor imagery-specific networks. The increased activity in precentral and frontoparietal networks in motor imagery might be used to control brain-computer interfaces to drive communication and limb prosthetic devices in patients with loss of motor control such as severely disabled amyotrophic lateral sclerosis patients in a locked-in-like state.

Depression and anxiety in individuals with amyotrophic lateral sclerosis: epidemiology and management.

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease with no curative treatment. Considering the devastating nature of the disease, a high prevalence of depression and anxiety in affected patients would be expected. A review of the literature shows prevalence rates for depression in ALS patients ranging from 0% to 44%, but studies using the structured interview according to DSM-IV criteria find highly consistent rates of 9-11%. Prevalence rates for anxiety in ALS range from 0% to 30%. Depression and anxiety appear to be not always properly addressed aspects of ALS, as there are only a few references in the literature about psychological and pharmacological interventions. Additionally, pharmacological antidepressant therapy is often not continuously monitored and its effectiveness remains unevaluated. A review of the literature and our own experiences show that there is a lack of psychological care and, to our knowledge, there is no specific psychological intervention method for ALS patients. Concerning pharmacological treatment of depression in patients with ALS, there is broad consensus among clinical experts that SSRIs and TCAs are helpful, but there have been no controlled clinical studies of these medications in ALS patients. TCAs can be prescribed if anticholinergic effects are desired simultaneously for treating pseudohypersalivation or insomnia. Anxiety is usually treated with anxiolytics, but again there have been no systematic studies of these drugs in patients with ALS. For psychological intervention we suggest a cognitive behavioural approach, which has to be integrated into an intervention programme that includes teaching of appropriate coping strategies and reappraisal skills and encourages engagement in activities that are still practicable and pleasant. We propose that the treatment of depression and anxiety should involve both cognitive behavioural therapy and pharmacological intervention. Pharmacological treatment should be strictly monitored for effectiveness. To date, no clinical trials are available that would allow us to recommend pharmacotherapy over psychotherapy or vice versa; however, evidence from other patient groups, such as elderly patients diagnosed with major depressive disorder, suggests that a combination of both therapies has the potential to also improve depression and anxiety in patients with ALS.

Emotional responding in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal disease, leaving the patient in a partially or completely deafferented state. In an explorative study, we investigated responses to visual socio-emotional stimuli in ALS patients. Pictures from the International Affective Picture System (IAPS) were verbally judged by 12 moderately affected ALS patients with a spinal onset and a slow progression and 18 age-matched controls, and data were compared with psychophysiological responses. Verbal emotional judgments of patients were more positive than ratings of controls. Regarding arousal, patients neutralized extreme pictures, in that they rated calm pictures as more exciting than controls and exciting pictures as more calm. These changes of emotional processing were unrelated to depression or frontal lobe dysfunction. There were no major differences between patients and controls concerning physiological responses to emotional stimuli. We conclude that emotional responses of ALS patients tend to be altered towards positive valence and towards a more balanced arousal state in early stages of the disease. These findings contradict assumptions of a generally negative impact of the disease on the emotional disposition and may indicate compensatory cognitive or neuroplastic changes.

Quantification of brain atrophy in patients with myotonic dystrophy and proximal myotonic myopathy: a controlled 3-dimensional magnetic resonance imaging study.

Myotonic dystrophy (DM1) and proximal myotonic myopathy (PROMM or DM2) are two distinct muscular disorders with multisystemic involvement. Both have previously been reported to be associated with cognitive impairment and white matter lesions detected by cerebral magnetic resonance imaging (MRI). In this study, the extent of brain atrophy was investigated in vivo in ten DM1 and nine PROMM patients in comparison to age-matched healthy controls for each group. The diagnosis was confirmed by DNA analysis of all patients. As a quantitative marker, the ratio of brain parenchymal to intracranial volume, called brain parenchymal fraction (BPF), was calculated from 3-dimensional MRI data using an automated analysis technique. Compared to age-matched healthy controls (mean BPF 0.852 +/- 0.032), the BPF in DM1 patients (0.713 +/- 0.031) was highly significantly decreased (P < 0.001). In contrast, the PROMM patients (mean BPF 0.792 +/- 0.029) showed only slightly decreased BPF values (P < 0.05). BPF was not significantly correlated to any of the clinical or genetic parameters in both diseases (disease duration, motor score, educational level, and number of CTG repeats in the expanded allele). In summary, global brain atrophy was demonstrated to occur in both diseases, but was more severely manifestated in DM1 patients.

Age-related brain parenchymal fraction is significantly decreased in young multiple sclerosis patients: a quantitative MRI study.

The extent of brain atrophy was determined in 33 patients with multiple sclerosis (MS) and in 60 healthy subjects (21-76 years) by calculating brain parenchymal fractions (BPF, the ratio of brain parenchymal to intracranial volume) from 3D MRI. Within the normal data base, subjects at higher ages showed significantly lower BPF values. In younger MS patients, BPF was significantly decreased compared with age-matched controls (20-29 years, p= 0.0022; 30-39 years, =p 0.0001; 40-49 years,p = 0.0444) and was significantly correlated with disease duration and disease severity, but not with the number of detectable MS lesions. Determination of age-related BPF demonstrated significant brain atrophy in early MS and can be considered as a useful biological marker for monitoring MS.