Existential decision-making in a fatal progressive disease: how much do legal and medical frameworks matter?

Background

Healthcare legislation in European countries is similar in many respects. Most importantly, the framework of informed consent determines that physicians have the duty to provide detailed information about available therapeutic options and that patients have the right to refuse measures that contradict their personal values. However, when it comes to end-of-life decision-making a number of differences exist in the more specific regulations of individual countries. These differences and how they might nevertheless impact patient’s choices will be addressed in the current debate.

Main text

In this article we show how the legal and medical frameworks of Germany, Poland and Sweden differ with regard to end-of-life decisions for patients with a fatal progressive disease. Taking Amyotrophic Lateral Sclerosis (ALS) as an example, we systematically compare clinical guidelines and healthcare law, pointing out the country-specific differences most relevant for existential decision-making. A fictional case report discusses the implications of these differences for a patient with ALS living in either of the three countries. Patients with ALS in Germany, Poland and Sweden are confronted with a similar spectrum of treatment options. However, the analysis of the normative frameworks shows that the conditions for making existential decisions differ considerably in Germany, Poland and Sweden. Specifically, these differences concern (1) the legal status of advance directives, (2) the conditions under which life-sustaining therapies are started or withheld, and (3) the legal regulations on assisted dying.

Conclusion

According to the presented data, regulations of terminating life-sustaining treatments and the framework of “informed consent” are quite differently understood and implemented in the legal setting of the three countries. It is possible, and even likely, that these differences in the legal and medical frameworks have a considerable influence on existential decisions of patients with ALS.

     

Modifications of the endosomal compartment in peripheral blood mononuclear cells and fibroblasts from Alzheimer's disease patients

Identification of blood-based biomarkers of Alzheimer''s disease (AD) remains a challenge. Neuropathological studies have identified enlarged endosomes in post-mortem brains as the earliest cellular change associated to AD. Here the presence of enlarged endosomes was investigated in peripheral blood mononuclear cells from 48 biologically defined AD patients (25 with mild cognitive impairment and 23 with dementia (AD-D)), and 23 age-matched healthy controls using immunocytochemistry and confocal microscopy. The volume and number of endosomes were not significantly different between AD and controls. However, the percentage of cells containing enlarged endosomes was significantly higher in the AD-D group as compared with controls. Furthermore, endosomal volumes significantly correlated to [C¹¹]PiB cortical index measured by positron emission tomography in the AD group, independently of the APOE genotype, but not to the levels of amyloid-beta, tau and phosphorylated tau measured in the cerebrospinal fluid. Importantly, we confirmed the presence of enlarged endosomes in fibroblasts from six unrelated AD-D patients as compared with five cognitively normal controls. This study is the first, to our knowledge, to report morphological alterations of the endosomal compartment in peripheral cells from AD patients correlated to amyloid load that will now be evaluated as a possible biomarker.     

Endoscopic perineal approach to the presacral space: a feasibility study

Background  Currently, pathologies from the presacral space are explored primarily by using transabdominal approaches. Major complications may occur, including bowel and rectal perforation, or bleeding. To avoid and reduce these potentially severe risks, a new surgical approach to the presacral space, which permits exploration through the perineum with minimal invasive techniques, had already been developed and is now further elaborated in a cadaver and clinical study. Study design  A prospective study was performed using four cadavers with no history of pelvic or perineal disease. A minimally invasive exploration of the presacral retroperitoneum was performed to examine a potential new anatomical surgical space. After positioning the patients in the prone or supine position, a 1-cm vertical median incision was made in the ano-coccygeal ligament. Entry to the presacral space was first established through blunt-finger and balloon dissection. A 30° 10-mm laparoscope was inserted through a 12-mm trocar, and two additional 5-mm trocars were inserted to avoid injury to the sciatic nerve. A clinical pilot study was performed on three patients using this technique. Results  Under direct vision, a wide dissected cavity was observed, with the rectum and mesorectum retracted ventrally. Access and manipulation of posterior pelvic organs were simplified. Placing cadavers in the jack-knife position provided superior accessibility to the presacral space when compared with a supine position. Clear exposure of the sacrum, mesorectum, ureters and bladder, prostate region, iliac vessels (with its branches), and lymph nodes was achieved. Conclusion  Endoscopic perineal approach to the presacral space was considered.     

Diffusion tensor imaging in early Alzheimer's disease

Our aim was to investigate the extent of white matter tissue damage in patients with early Alzheimer disease (AD) using diffusion tensor magnetic resonance imaging (DTI). Although AD pathology mainly affects cortical grey matter, previous magnetic resonance imaging (MRI) studies showed that changes also exist in the white matter (WM). However, the nature of AD-associated WM damage is still unclear. Conventional and DTI examinations (b=1000 s/mm(2), 25 directions) were obtained from 12 patients with early AD (Mini Mental State Examination [MMSE] score=27, Grober and Buschke test score=33.2, digit span score=5.6) and 12 sex- and age-matched volunteers. The right and left mean diffusivity (MD) and fractional anisotropy (FA) of several WM regions were pooled in each patient and control, and compared between the two groups. Volumes of the whole brain and degree of atrophy of the temporal lobe were compared between the two groups. In AD, MD was increased in the splenium of the corpus callosum and in the WM in the frontal and parietal lobes. FA was bilaterally decreased in the WM of the temporal lobe, the frontal lobe and the splenium compared with corresponding regions in controls. Values in other areas (occipital area, superior temporal area, cingulum, internal capsule, and genu of the corpus callosum) were not different between patients and controls. No correlations were found between the MMSE score and the anisotropy indices. Findings of DTI reveal abnormalities in the frontal and temporal WM in early AD patients. These changes are compatible with early temporal-to-frontal disconnections.     

Brain responses to emotional stimuli in patients with amyotrophic lateral sclerosis (ALS)

Amyotrophic lateral sclerosis (ALS), a progressive motor neuron disease, affects movement and communication abilities and emotional processing. Subjective ratings of emotional stimuli depicting social interactions and facial expressions differed significantly between ALS patients and healthy controls in a previous study with a reduction of negative emotional valence (pleasantness) and lower subjective arousal (excitement) in ALS patients. In the present study, sixty similar emotional slides were presented to 13 ALS patients, 15 matched healthy controls and six tetraplegic patients. Subjective reports of valence and arousal as well as brain responses to the affective pictures using functional magnetic resonance imaging (fMRI) were measured. The picture series was presented twice with a 6-months interval to investigate effects of disease progression. ALS patients presented an increased brain response in the right supramarginal area and a reduced brain response in extrastriate visual areas at both measurements compared with healthy controls. Within the ALS patients' group a reduction of brain responses in the anterior insula at the follow-up was correlated with the subjective arousal. The reduced response in the anterior insula is tentatively interpreted as indicating reduced arousal during the course of the disease at the neural and behavioural level. The reduction of activity in extrastriate visual areas might be similarly interpreted. The increased brain response in the right supramarginal area of ALS patients might represent an altered sensitivity to social-emotional cues.