Jan Bernheim

A survey on self-assessed well-being in a cohort of chronic locked-in syndrome patients: happy majority, miserable minority

Objectives Locked-in syndrome (LIS) consists of anarthria and quadriplegia while consciousness is preserved. Classically, vertical eye movements or blinking allow coded communication. Given appropriate medical care, patients can survive for decades. We studied the self-reported quality of life in chronic LIS patients. Design 168 LIS members of the French Association for LIS were invited to answer a questionnaire on medical history, current status and end-of-life issues. They self-assessed their global subjective well-being with the Anamnestic Comparative Self-Assessment (ACSA) scale, whose +5 and −5 anchors were their memories of the best period in their life before LIS and their worst period ever, respectively. Results 91 patients (54%) responded and 26 were excluded because of missing data on quality of life. 47 patients professed happiness (median ACSA +3) and 18 unhappiness (median ACSA −4). Variables associated with unhappiness included anxiety and dissatisfaction with mobility in the community, recreational activities and recovery of speech production. A longer time in LIS was correlated with happiness. 58% declared they did not wish to be resuscitated in case of cardiac arrest and 7% expressed a wish for euthanasia. Conclusions Our data stress the need for extra palliative efforts directed at mobility and recreational activities in LIS and the importance of anxiolytic therapy. Recently affected LIS patients who wish to die should be assured that there is a high chance they will regain a happy meaningful life. End-of-life decisions, including euthanasia, should not be avoided, but a moratorium to allow a steady state to be reached should be proposed.

Locked-In Syndrome in Children: Report of Five Cases and Review of the Literature

The locked-in syndrome is a rare neurologic disorder defined by (1) the presence of sustained eye opening; (2) preserved awareness; (3) aphonia or hypophonia; (4) quadriplegia or quadriparesis; and (5) a primary mode of communication that uses vertical or lateral eye movement or blinking. Five cases are reported here, and previous literature is reviewed. According to the literature, the most common etiology of locked-in syndrome in children is ventral pontine stroke, most frequently caused by a vertebrobasilar artery thrombosis or occlusion. In terms of prognosis, 35% of pediatric locked-in syndrome patients experienced some motor recovery, 26% had good recovery, 23% died, and 16% remained quadriplegic and anarthric. These findings raise important ethical considerations in terms of quality of life and end-of-life decisions in such challenging cases.

Global Progress I: Empirical Evidence for ongoing Increase in Quality-of-life

This paper argues that both the relativist and the pessimist critiques of the idea of progress are inadequate. Progress is defined as increase in global quality of life (QOL). Such QOL is intrinsically subjective, but not relative. It can be reliably measured through “life satisfaction”-type questions. The “World Database of Happiness” provides extensive data on social, economic and psychological factors that correlate with overall QOL. They include wealth, health, security, knowledge, freedom and equality. Various statistical data suggest that all these QOL indicators have undergone significant improvements during the last half century, in most of the world. This gives strong support to the thesis that progress objectively occurs.

Le Locked-In Syndrome : la conscience emmurée

INTRODUCTION The Locked-In syndrome (LIS) is defined by: (i) the presence of sustained eye opening (bilateral ptosis should be ruled out as a complicating factor); (ii) preserved awareness; (iii) aphonia or hypophonia; (iv) quadriplegia or quadriparesis; and (v) a primary mode of communication that uses vertical or lateral eye movement or blinking. Acute ventral pontine lesions are its most common cause. Following such brainstem lesions patients may remain comatose for some time and then gradually awaken, remaining paralyzed and voiceless, superficially resembling the vegetative state. BACKGROUND It has been shown that more than half of the time physicians fail to recognize early signs of awareness in LIS. Given appropriate medical care, life expectancy may be several decades but the chances of good motor recovery remain small. Eye-controlled computer technology now allows LIS patients to communicate and control their environment. Recent studies show that most LIS patients self-report meaningful quality of life and the demand for euthanasia is infrequent. CONCLUSION Patients suffering from LIS should not be denied the right to die--and to die with dignity--but also they should not be denied the right to live--and to live with dignity and the best possible pain and symptom management and revalidation.

Locked-in: don’t judge a book by its cover

Amyotrophic lateral sclerosis (ALS; also called motor neuron disease) is a devastating medical condition that progressively robs patients of their ability to move, speak and eventually breathe. At present, many physicians are hesitant to propose tracheostomy and respiratory support in the terminal phase of ALS. In accordance with the principle of patient autonomy, physicians should respect the right of the ALS patient to accept or refuse any treatment, including mechanical ventilation. Also, in environments where euthanasia or physician-assisted death is legal, such requests can be acceptable. At least two conditions are necessary for full autonomy. To have a claim on full autonomy, people need to have intact cognitive abilities, and to exercise this right they must be able to communicate. In the past, the first condition was in doubt (indeed, overlap with other neurodegenerative diseases is sometimes suspected and some patients with ALS are thought to have associated frontotemporal dementia) and the second was severely compromised in patients with devastating motor impairment (communication being limited to the twitch of a finger or the blink of an eye). In this issue of J …

Synthesis and in Vitro Antineoplastic Activity of Diorganostannylene Derivatives of 2,6-Pyridine Dicarboxylic Acid

The widespread success of platinum compounds in the clinical treatment of testicular and ovarian cancers for instance, has stimulated research in the area of metal-based anti-tumour drugs and spurred the search for organometallic compounds with improved therapeutic properties.

The role of fluorinated pyrimidine analogues in the induction of the in vitro expression of the fragile X chromosome

SummaryThe modes of action of 5-fluoro-2′-deoxyuridine (FdUrd) and 5-fluoro-2′-deoxycytidine (FdCyd) were studied in PHA-stimulated lymphocytes from normal volunteer donors and a fragile X patient. In both cell types, FdUrd and FdCyd inhibited cell proliferation at concentrations of 3x10-8M. Thymidylate synthetase was identified as the decisive target for the action of both FdUrd and FdCyd, as judged from the following observations: First, addition of thymidine to the culture medium was able to counteract both FdUrd and FdCyd toxicities, whereas addition of dCyd had no observable effect. Second, inhibition of the in situ thymidylate synthetase activity measured as an increase in the level of [3H]-dThd incorporation coincided with the inhibition of cell proliferation. Third, the inhibition of the thymidylate synthetase-dependent incorporation of [3H]-dUrd into newly synthesized DNA coincided with the inhibition of cell proliferation. The effects of FdUrd and FdCyd on the in vitro expression of fragile site Xq27 of fragile X chromosomes was shown to be based on the depletion of the intracellular pool of thymidine-5′-monophosphate (dTMP), as fudged from the following observations: First, both the FdUrd- and FdCyd-dependent induction of site Xq27 coincided with the antiproliferative effects of the respective fluoropyrimidines. Second, addition of thymidine (dThd) to the culture medium both prevented the expression of site Xq27 and neutralized the cytotoxicity of FdUrd and of FdCyd. On the basis of these findings, we provide further evidence for the concept that the fragile X site is located in an AT-rich region.