Requiem.

"In never considering neuromuscular disease to be untreatable, Yves Rideau has found ways to ameliorate every aspect of these conditions. His work has resulted in immeasurably enhancing the quality of life of his patients". This dedication included into the Guide to Evaluation in Management of Neuromuscular Diseases, 1999, made by a coworker who studied in Poitiers from 1981 to 1983, summarizes the content of this paper.

"No longer knowing where the sun rises, nor where it hides underground, we must hurriedly deliberate" (according to The Odyssey, Song X, verses 190-192, Aiaié, Circé's field).

Introduction

"I", the personal pronoun, is seldom used in medical publications, particularly of the statistical variety. However when we strive to explain the intimately individual meaning of a lifelong commitment that is drawing to a close, its use is to be preferred. I am also determined, on this unique occasion, to thank and honor all those who assisted me, often discreetly, and thereby allowed me to move forward as I tried to comprehend a particularly difficult pathology.

My initial contact with muscular dystrophy, especially with the Duchenne type (DMD), symbolized the abnegation of the caregivers of the time (Fig. 1). The isolation of the diseased children in specialist centers constituted the basis of the recommendations in France during the 1970s. For this reason, five of them were permanently hospitalized in the medical rehabilitation department of Poitiers hospital, on the hope that contemporary techniques could counteract some of the disease's deleterious effects. The first lesson received at that time was the result of a family's revolt: "Where do you get the right to deprive my brother of what's left of his freedom during the little time he has still to live?". My response consisted in stressing the exigencies of an optimal medical care. Shortly thereafter, the boy passed away. That was when I realized that I needed to modify my approach and my techniques.

Figure 1.

Body status seen in the 1970s in an adolescent suffering from a very rapidly evolving DMD; death at the age of 16 years.

The rare studies insisting on a comfortable life for DMD patients originated for the most part in the United States. They carefully attempted to prolong the ambulatory stage by bracing, after a surgical correction which was contraindicated in France. The eminent defender of this kind of management in the 1960s, Paul J. Vignos, was in charge of the one of the medicine departments of the University of Cleveland, Ohio. The initial rule that he promulgated, firmly excluded prolonged bedrest: "The duration of enforced immobilization in bed or in a wheelchair should be kept to a minimum during an intercurrent acute illness [...] This allows an active physical therapy program to be prescribed that will help minimize disuse atrophy [...] This prescription, for such a combined activity program, should be given to neuromuscular disease patients if it is anticipated the illness will require bedrest for longer than 4-5 days".

I was fortunate enough to be introduced to this country in 1972 thanks to professor A. Cournand, from the Columbia University, winner of a medicine Nobel Prize for his work in the cardio-respiratory area and for his discovery of cardiac catheters. Following my requests, he informed me that I needed to start by observing carefully the problems I wished to solve, without thereby neglecting the patient in his integrity. He affirmed that "when knowledge of the clinical course became clear, therapeutic decisions would come much more easily". He then advised me to visit a specialized unit devoted to respiratory assistance in Goldwater Memorial Hospital, which was part of the New York University Medical Center. In that I saw, among many poliomyelitis patients, three DMD bedridden boys surviving thanks to permanent assisted ventilation and supervised by M. Solomon. Exchanges of concepts subsequently occurred; in 1973, Solomon came to Poitiers to gather information on the procedures we were employing at that time.

A general consensus underlined the inexorable characteristic of the disease. Knowledge of the condition of the wheelchair-confined patients was minimal. That is why I spent long periods in Montreal for one decade, where I had the possibility to regularly supervise one hundred patients who never benefited from even the slightest palliative management. They were allowed to live in accordance with their wishes and consequently they incarnated the natural course of the disease. This activity led to my residing in Montreal from 1977 to 1979, at the University Rehabilitation Institute. During this fruitful period, I studied the management practices, implemented in the main institutions, that respected the principles put forward by G.E. Spencer and P.J. Vignos (e.g. m. tibialis posterior transfer, by D.A. Gibson in Toronto and J.D. Hsu in Los Angeles, taught to me by my dear fellow Louis Roy in Quebec; exceptional recourse to scoliosis surgery, also in Toronto and Los Angeles). My stay in Montreal was much more important for me, because, in collaboration with Raymond Lafontaine, a well-experimented pediatrician, we created in 1978 the first local myopathic clinic, at the Saint Justine Hospital. His vision on the handicaps was a revelation for me, and I wish to quote him: "Of course, correction of a physical impairment is important, but it does not avoid the disappointment of a child who sees his strength continue to diminish. What matters most is to teach him how to accept his disability. The true way of reaching this goal consists in enabling him to develop all his intellectual faculties in such a way as to lead his life on his own". In order to respect his advice, it was first of all necessary to refute the non-reversing fatal prognosis of DMD patients, which was far from being the case at that time.

For the recognized authorities on neuromuscular diseases, many of whom were English, the promise of survival was unthinkable:

"Tracheostomy or long-term ventilation, even on an intermittent nocturnal basis, are rarely justifiable" (John Walton, in Disorders of Voluntary Muscle, University of Newcastle, UK, 1981).

"Perhaps I might end by saying that I feel strongly that tracheostomy should be avoided in patients with muscular dystrophy. It prevents the patient from being allowed to die in peace when the disease progresses to bulbar failure, which should remain as the final point" (personal letter from a specialist of a Respiratory Unit, Saint Thomas Hospital, London, November 1983).

"Intermittent positive pressure ventilation with a nasal mask is an important recent advance which may have useful application to Duchenne Muscular Dystrophy [...] A potential advantage of ethical importance is that prolongation of life beyond the point of incapacitating bulbar weakness is less likely than with tracheostomy" (in British Medical Bulletin, Management of children, Jerry Lewis Neuromuscular Research Center, London, UK, 1989).

These references illustrate the widespread assertion of the conventional wisdom according to which the course of DMD is ultimately prolonged on the muscles commanded by the bulbar, which controls the functions of speaking, eating, deglutition, etc. This condition would clearly not be compatible with therapeutic attempts to prolong life at all cost. It was in that context that I decided to resume my activities in Poitiers, where I was sure to find the goodwill and devotion necessary to progress, even with little outside support, in what constituted a human as well as a medical clinical research. I remain deeply grateful to the entire staff of the rehabilitation medicine department, and also particularly to Ph. Boutaud, M. Morin, B. Potocki, and our first-rate surgeon, Gérard Duport.

It was in that environment that we deemed it indispensable to anticipate first early and efficient correction of orthopedic deformities without bracing, and then recourse to the use of mechanical respiratory assistance in order to check up the classic restraints of the DMD course. It was more specifically in this framework that a simplified ventilation method, readily accessible to a wide range of patients, was set up in Poitiers using the nasal tract throughout the night for the first time anywhere. The minor clinical decrease of this major vital function observed as of 1984 constituted a genuine and fortunate breakthrough, even if its long term effects were incomplete. The introduction of ventilation as a regular treatment for the sick children was reinforced by two lonely initiatives allowing some assisted patients to return to their homes and even create their own families (Gérard Gatin, Institut Saint Jean de Dieu, Paris and Bud Curran, Executive Office of Human Services, Lakeville Hospital, Massachusetts).

However, the crucial point in our experience, of which the first publication dates from 1986, stipulated the necessary complementarity of the two paths of access, nasal and tracheal, meant according to the severity of respiratory insufficiency. This principle was favorably received internationally, although unexpected obstacles were soon raised in my own country. Fortunately, several outside cooperation programs had already been developed, and they facilitated the normal pursuit of our research. Since the 1980s, one of these exchanges outclassed the others: it was based in Italy, at the University of Naples, Cardiomyology and Myology Service, with the active encouragement of Professors Giovanni Nigro, Lucia Ines Comi and Luisa Politano. This specialist department regularly managed a large number of neuro-muscular patients and made it a constant priority to ease their suffering, thereby ensuring a permanent link with the similar practices pursued in Poitiers. The final phases of our work would have never been carried out over the last ten years without the warm welcome I personally received in what became, in many ways, my intimate second family. The most recent advances achieved during this period should be considered as work carried out by our interconnected energies.

If the preceding chronological sequences are meant to render homage to the unfailing collegiality of those mentioned, they are also aimed at leading to proof validity and transmission of some ultimate principles addressed to as large a population as possible. I can affirm with certainty the following points:

Effective stabilization of the DMD course is henceforth available, at its adult stage, and this primarily was seen after early protection in the most severe cases of patients affected by this pathology (Fig. 2).

Figure 2.

Diagram of the modified course of a particularly severe DMD case (the dotted line represents the evolution on a non-treated control group). Life expectancy was particularly short, in spite of nasal ventilation and other palliative measures (o). Intermittent anticipated tracheal ventilation was proposed for the first time against the lethal issue. Stabilization has been observed over a number of years, constituting the initial clue of effectiveness noticed more than ten years ago.

Use of tracheostomy may and must be rendered easily accessible when indicated since it constitutes the single means of ensuring the effectiveness and safety necessary with regard to the prolongation of the most threatened lives (Fig. 3). On this subject, thanks to our cooperations a new concept has been developed; it is based on an ostium constituting a "tracheal nostril", and it minimizes the presence of a permanent and often stiff tube in the throat (special canula developed with the help of German correspondents, particularly Andreas Hahn, a neuro-pediatrician from the University of Giessen). This project followed a protocol unanimously accepted by the multidisciplinary medical council of Naples in May 2006.

Figure 3.

Another example of tracheal respiratory assistance in a child also suffering from a very severe DMD, even though all the recommended orthopaedic and therapeutic measures were carried out in a timely manner (stop of walking at 7 years, 9 months [on the left]; progressive respiratory deficit already observed at the age of 5 years, justifying early indication of nasal ventilation at the age of 9 years and tracheal ventilation imposed after a serious bronchopulmonary infection [on the right]).

Complementary publication concerned: Corrado A, Gorini M, De Paola E. Alternative techniques for managing acute neuromuscular respiratory failure. Semin Neurol 1995;15:84-7 (when an obstructive pulmonary infection occurs, with hypercapnia and hypoxemia, a more suitable mechanical ventilation is necessary, as well as oxygen supply and appropriate antibiotic therapy).

The desired global stabilization has already existed for ten years, thereby rendering possible a satisfactory quality of life. The evidence of a definite progress consists in the doubling of classical life duration.

Our experience conclusively demonstrates that when an alteration of the respiratory function is detected, the therapeutic goal of "giving air to breathe" is obvious [see appendix].

Up until now the dystrophic process has never extended to all the voluntary muscles at the end of the disease's course. On the one hand, it is clear that progressive muscle weakening involves specific muscles according to an astonishingly constant distribution, and that the weakening increases during the growth stage in each individual. On the other hand, some muscle territories would appear, with equally different distribution, to be spared, for instance those in relation with the troncus encephalicus and the perineum sphincters. The notion of an implacable and permanent tenet of the disease is consequently inaccurate. Besides, it does exist neglected variations in DMD gravity, nevertheless described as an "intermediate form" since the end of the 1970s, confirmed in a famous dystrophin study, published in the New England Journal of Medicine in 1988. These notions have direct influence on the comprehension for treatment to be respected and applied.

Why have I chosen the title "Requiem"? Not only for the successive involvements of physicians who have combated this emblematic disease of inexorability, but rather for the sake of the children and their families always set out in pursuit of more peaceful existence.

Seeing that basic research constantly ensures a proximate care, now if ever, is the time to enforce the life-saving objective of the waiting patients. In this connexion, one must assert that a rude mistake is being committed when specific caretaking principles are not respected (Muscular Dystrophy, incurability, eugenics, in Acta Myol 2007;XXVI:22-32). And now it is the interests of one and all that clinical medical progress already available may be improved and sustained by others.