The purpose of this interview is to explore his character for our members and readers The Rizzoli Orthopaedic Institute in Bologna boasts a prestigious nation-wide reputation. In dealing with rare neuromuscular diseases, the approach becomes a complex one, as in any specialist field. However, Cesare Faldini (click here), a well-known authority to many of us, stands out for his determination and competence, particularly evident in his ongoing orthopaedic studies in the field of muscular dystrophies. The purpose of this interview is to delve into his profile for our members and readers.
We have already mentioned your role at the Rizzoli Orthopaedic Institute as an orthopaedist, professor and researcher, but would you like to enlarge on this description?
My name is Cesare Faldini and I am the Director of the Orthopaedic and Trauma Clinic 1 at the Rizzoli Orthopaedic Institute, affiliated with the University of Bologna. My connection with Luciano Merlini dates back to the period of my thesis in orthopaedics. Later, at the end of my studies, I joined Rizzoli, where I had the opportunity to collaborate with this extraordinary researcher. Merlini is a unique individual who turned orthopaedic challenges into opportunities to study neuromuscular diseases. Until the 1950s-60s, neurologists focused on other pathologies within the large neurological institutes, such as strokes and Parkinson’s disease. Dr Luciano Merlini, finding himself immersed in an orthopaedic environment at Rizzoli, focused his attention on neurological diseases with orthopaedic consequences, turning a supposed limitation into an opportunity. His experience is considered unique worldwide and arouses the admiration of scholars around the globe.
The Rizzoli Orthopaedic Institute, founded in 1896, was the first in the world to separate orthopaedics from general surgery, an initiative that helped define Bologna as the cradle of orthopaedic surgery. In 1905, the English Orthopaedic Society was founded in Bologna, in full recognition of the Institute’s pioneer role. This allowed Rizzoli to attract, for more than 125 years, patients with orthopaedic deformities deriving from various pathologies, thereby consolidating its reputation on both a national and international level. Professor Merlini has succeeded in taking full advantage of this unique resource, turning challenges into unprecedented study opportunities.
In the 1990s, I had the honour of joining Rizzoli while Merlini was already actively involved in his role. Thanks to his extraordinary case history and my passion for research, I requested to collaborate with him. My mentor, Professor Sandro Giannini, former Director of Orthopaedic Clinic 1, told me that Merlini would enrich my field of knowledge, he himself being a true scientist in the medical field. But what do scientists do in the medical field? Medical scientists, with great humility, carefully observe patients and draw common rules for treatment from their characteristics. Any process based on observation requires such humility, as observation is the key to learning. Working with Dr Merlini, I learnt to observe carefully. Our collaboration was a fruitful one: Merlini contributed his expertise in diagnosis, while I developed my skills in surgery. Together, we achieved extraordinary results, combining our knowledge in a synergetic union.
So before your meeting with Merlini, to what extent had you dealt with neuromuscular pathologies?
Muscular dystrophies are a constant presence in orthopaedic surgery, albeit in a sporadic form. However, their rarity presents a significant challenge. Without a specialised centre and a constant flow of cases, developing in-depth expertise is particularly complex. As you can imagine, for example, every two years a patient comes in with a specific problem, the doctor observes him but cannot give a very precise answer because he lacks developed expertise. The heritage has been to create a system and bring a large number of cases together. Each patient is part of the solution, each patient produces a piece of knowledge to cure not only him/her but also those who will come after.
Another ongoing study is: ‘3D modelling of muscle-tendon units to identify tissue interaction in muscular dystrophies and ageing (3D-MTU)’ by Vittoria Cenni and Patrizia Sabatelli from CNR Bologna with the team led by Paolo Bonaldo from the University of Padua. What is your role in this?
Our collaboration with Dr. Merlini has allowed us to obtain funding for projects and to contribute to the genetic characterisation of Ullrich muscular dystrophy, focusing on issues of autophagy and collagen VI alteration. At our centre, we collect muscle and fat tissue samples from patients and send them to the laboratories. This project has led to the creation of a field of expertise that I proudly define as unique worldwide. We have obtained funding for four projects from the Ministry of University and Research, which have contributed to the genetic characterisation of this serious disease.
My collaboration with Dr. Merlini has also been enhanced through a collaboration with Prof. Paolo Bonaldo of the University of Padua, who is an internationally renowned collagen VI expert (read Paolo Bonaldo’s interview, click here). This collaboration has enabled us to win projects and contribute to typifying the whole genetic part of Ullrich muscular dystrophy by focusing on autophagy and collagen VI alteration issues. Our team at Rizzoli takes muscle tissue and fat tissue samples from our patients and, by sending them to the labs, we followed the process and made a ‘match’ between the visible clinical condition and the results of Prof. Bonaldo’s exceptional observations and Prof. Merlini’s neurological considerations. The result was a field of experience that I proudly call unique in the world. We have won 4 projects from the Ministry of University and Research with which we have contributed to typifying the genetics of this serious disease (For the excellent explanation of this study project read the interview with Dr. Vittoria Cenni, click here).
We know that you have written a monograph on degenerative scoliosis. One of the effects of Collagen VI deficiency disorders is precisely the onset of scoliosis, which is inevitably degenerative. Please give us a brief explanation of the difference between idiopathic scoliosis and neuromuscular scoliosis.
Scoliosis means that the spine seen in a perfectly straight frontal plane begins to curve. It is a very complex pathology and has many origins. In the majority of cases the cause is unknown, and in this case we are talking about idiopathic scoliosis, where the scoliosis typically starts to curve with the onset of growth and stops when growth is completed. By intuition, the earlier it appears, the more severe it is. If it appears only a year before the end of growth it will remain within a few degrees, if, on the other hand, it appears at 6 years of age it may worsen over the course of the long growth span. Scoliosis worsens according to the doubling rule in the sense that every year, if left untreated, it doubles. The first doubling is not scary, also because an under 10 degrees scoliosis is non-existent, so calling any curve under 10 degrees scoliosis would be a mistake.
Our Heavenly Father did not use a goniometer when he created us. Forms from 10 to 20 degrees are mild forms that need no treatment. Treatment begins from 20 degrees onwards. Forms ranging from 20 to 40 need to be cured. Above 40 they are severe. Then there is the opportunity for surgery. In short, the first doubles are harmless, from 2 you go to 4 and then 8. The first years of scoliosis are non-consequential. The problem is that then it goes from 8 to 16 and then to 32. The next doubling launches us into the need for surgery. Within 5 doubles there is full-blown scoliosis. Now it is clear that a patient has to be intercepted and kept under observation only when he/she has scoliosis below 16 degrees, at which point he/she needs to be treated to avoid going from 16 to 32. Then if the scoliosis goes from 32 to 64 or beyond, one has to think in terms of surgery. This is the role of prevention, screening and medicine.
This same rule also works in neuromuscular diseases, with a few differences. In neuromuscular conditions there is an imbalance of forces and therefore some muscles on one side stretch more with respect to the other, so there is a known efficient cause. Neuromuscular disease is active from the moment of birth and scoliosis can become a very serious issue, for the main reason that if the muscular dystrophy does not create an imbalance the spine remains straight but, as you know, not all muscles are affected in the same way, order and magnitude. When the muscle is affected by dystrophy the rule is that it worsens at a considerably faster rate compared to idiopathic scoliosis.
When this asymmetry arises, the curve is very fast. Moreover, since we are talking about long muscles, also including the pelvis, in neuromuscular scoliosis the pelvis behaves as if it were a vertebra and also rotates together with the spine and this is a major problem! The imbalance of the pelvis makes it difficult for a patient to sit and, if the pelvis tilts, one leg seems longer and one shorter. For a patient sitting on one buttock this is uncomfortable and there is a need for a brace, a lateral support given the tilt/balance. These conditions obviously constitute the specific differences between idiopathic scoliosis and neuromuscular scoliosis. Another characteristic of neuromuscular scoliosis is that, if it is intercepted when it starts to double, it is very elastic; it is even much more elastic than idiopathic scoliosis, so the effort to straighten it is far less even at the surgical level. There is this ‘golden time’ when the scoliosis starts and the patient is already in the wheelchair and he/she feels that he/she starts leaning to one side. Getting him/her straight again with surgery is less burdensome. If I leave things as they are, they stiffen up over time and surgery will become more challenging.
So no neuromuscular scoliosis remains elastic?
Initially, they all show some degree of elasticity, but over time they all tend to stiffen. This is an intrinsic feature of human evolution.
We know that wearing a back brace is recommended; this is sometimes corrective and sometimes provides maintenance over time. I suppose in our cases it is mostly the latter, or am I wrong? Does it depend on the type of scoliosis, the medical history and the materials involved? Please shed some light on this for us.
The back brace is corrective. If I put a back brace on a child with 16 degrees of scoliosis and if he/she remains at 16 degrees in that year, how far have I corrected him/her? 16 degrees, because according to the doubling rule he/she was supposed to make 32 but didn’t! That’s called correction! In all scolioses the back brace is put in to interrupt this chain that proceeds according to the power of two, because bear in mind that when I put a back brace on a child who has 4 years of growth we remember the doubling 16, 32, 64,128! We cannot leave the patient to his/her own devices. It’s dangerous! If in 4 years of bracing I have only doubled from 16 to 32 I will have gained 96 degrees of correction. An ideal brace worn at an ideal time will stop deterioration.
The problem is that nobody stays in a back brace 24 hours a day. We know that treatment with a back brace slows down the worsening of scoliosis depending on the shape of the patient, his/her breathing capacity, his/her cooperation, the family that helps and motivates him/her; there are so many parameters that make a back brace portable. The back brace is an opportunity that, however, must be tailored to the patient. No one is to blame. There is a worsening trend that depends on the patient and the ability to wear it. The optimum is to arrest the curve and stop it doubling. Of course it is easier to intervene in puberty when there is no worsening power in the neuromuscular pathology and the muscles are unbalanced. It has to be said that the brace is not always an asset because, if I have a patient who is still ambulatory but has very little strength, he/she has balance problems and maybe has a reduction in the size of the rib cage. If he/she were to wear the brace, he/she would lose the ability to walk because of the additional weight. Here the choice lies between back brace or surgery. The scoliosis that would continue in the absence of the back brace would give him/her problems with a distorted pelvis, closing of the chest, etc. The choice is difficult but the stakes are high.
When the neuromuscular patient is fitted with the brace, does he/she not lose the strength of the chest muscles? Does he/she not become dependent on the back brace to the point where he/she can no longer remove it even on the beach?
When a patient with a neuromuscular disorder wears a back brace, he or she does not necessarily lose the strength of the chest muscles. The purpose of the back brace is to prevent deformation of the spine through the muscles that have not yet been compromised. In the context of neuromuscular diseases, it is muscle weakness that causes the curvature of the spine, and the brace intervenes precisely to counteract this imbalance. In theory, if both muscles were paralysed, scoliosis would not occur. However, the reality is more complex as the muscles tend to weaken in a non-uniform manner. Therefore, not all patients can tolerate the use of a back brace, and each one has a unique medical history. It is important to avoid extreme approaches, such as saying ‘back brace or death’, as not everyone is suited to this solution, just as it would be wrong to categorically state ‘I will never wear it’, if we consider that surgery presents other complications. We must be cautious. Watch out.
Dr Merlini, could you kindly answer the same question?
The loss of strength of the muscles that support the spine and lead to scoliosis depends on the basic disorder. Whether wearing a back brace leads to a decrease in muscle strength has never been scientifically proven to my knowledge. The function of the back brace in muscular scoliosis is twofold: to allow a more comfortable sitting position and to reduce the progression of the curvature of the scoliosis.
The first objective is achievable and can often be maintained for a long period. It is the solution in cases where the operation is too risky or when the useful time has passed. The tolerability of the brace in these cases depends on various factors, not least on how well it is has been made and fitted. Let us not forget that the brace is an artefact and the quality of the craftsman, especially in difficult cases, makes all the difference.
Therefore, we cannot generalise but we can safely say that a good back brace can be a useful solution in certain cases to achieve a comfortable sitting position. Unlike surgery that permanently corrects scoliosis, the brace only corrects the scoliotic curve when it is worn. Once the back brace is removed, the scoliosis returns to its original position. So it can be said that the corset ‘masks’ but does not correct scoliosis. Saying that the back brace reduces the progression of the muscular scoliosis is like saying that it strengthens the spinal muscles, and this too is a statement that has no scientific basis.
To what extent do physical activity and physiotherapy influence it?
From the point of view of the angle of the curvature, no physical activity has been shown to influence the evolution of scoliosis. However, physical activity is fundamental for general well-being. Good muscle tone improves physical endurance and the ability to move. Physiotherapy, together with muscle strengthening, is essential to maintain the residual function of the unaffected muscles and to improve respiratory capacity. In addition, physiotherapy helps balance the body and improve posture. Although it does not directly affect the angle of the scoliosis, it contributes significantly to the patient’s general well-being. It creates balance and static exercises but has no effect on the angle of the scoliosis.
In the case of severe curves, selective corrective arthrodesis of the spine using pedicle screws and titanium rods is commonly performed. What does it consist in?
Corrective arthrodesis surgery has changed completely because, when I started my work as an orthopaedist and my collaboration with Merlini, to operate on a scoliosis you had to put hooks in the vertebrae and then you put one at the top and one at the bottom of the spine and these hooks were connected with steel rods and pulled, so the hook was on one vertebra at the bottom and one at the top. This meant that the pulling force was low and that for about 3 to 6 months a patient with a jerk or a movement could technically unhook one vertebra and have to be operated on. Today, thanks to the evolution of the technique with connected titanium rods attached to each vertebra with a screw, the spine can be perfectly straightened.
This surgery succeeds best when the curve is intercepted in the elastic phase, and although we now have instruments to correct even rigid scoliosis, the stiffer the spine, the more aggressive you have to be in the operating theatre. The neuromuscular patient is a delicate patient so the lighter you are the less complications there are. In rigid curves, correction involves removing a segment of vertebra. Bear in mind that we were the first in the world to perform this operation to remove the segment of vertebra. Few centres do this. It is very risky and you have to sign a very high risk consent, the average duration is 10 hours and every hour you need a transfusion. It entails a prolonged awakening in intensive care 2 or 3 days after the operation. This is the opportunity for those who have progressed to a hard curve and waited too long. The surgeon is committed to counteracting a problem and you can imagine the impairment of internal organs due to the curve compressing them.
This operation has a mortality rate, and it is not a matter of inexperience, negligence, or bad performance on the part of the surgeon. It has always gone well for us, but other centres report a mortality rate of 5%. The fact that it has never happened with us does not mean that the risk is not there. It is a choice that must be made consciously without being catastrophic and with realism. It is the most complicated surgical procedure in general. From an anaesthesiological point of view, our anaesthetists have compared it to a liver transplant.
Have there been cases where surgery has been impracticable for reasons unrelated to the patient’s will?
You cannot generalise. There is no universal answer to this question. Every patient is unique and brings with him or her their own medical challenges. When dealing with a problem of scoliosis, it is essential to consult a specialised centre, where a competent team works together to assess each individual case. At our centre, for instance, the contribution of Dr Merlini, although now in retirement, remains crucial due to his vast experience and knowledge. The decision regarding the operation depends on the team’s overall assessment: if the scoliosis is elastic, the operation may take less time (e.g. 4 hours), whereas if it is only partially elastic, it may take longer (6-7 hours). However, in cases of rigidly advanced scoliosis, where parts of the vertebrae have to be removed, this entails significant risks that other centres could avoid. We are the only centre that does this because this operation has a risk coefficient that others do not feel comfortable with. When the risks outweigh the potential benefits, our team may decide that surgery is not the best option for the patient.
One of the girls in our group who helped me prepare the questions told me that she had undergone surgery. She had complications with being intubated, but was satisfied with the surgery for about three years: then the problems gradually began again. First hip pain, then recently back pain. The surgery went well and the bars are still in place today, however the vertebrae continued not to bend but to rotate. She was advised to have joint infiltrations to combat the pain. What do you think about infiltrations in non-idiopathic cases?
I don’t know. It is such a complex clinical condition where you have to study the patient in depth to find the solution. The way out. We are talking about an extremely personalised condition that cannot be generalised. Usually those who perform operations of this kind have wide expertise. She should consult those who are treating her and let them find a solution for her.
Would you like to talk about any class of muscle relaxants that can decrease stiffness, even if they do not specifically target people with Collagen VI deficiency by not acting at the root of the problem? Can a muscle relaxant actually help or are there side effects that would be considerable in our case?
I invite you to discuss this with Prof. Merlini. I am a carpenter!
Dr Merlini, could you kindly answer this question?
In myopathies, the elastic muscle fibres lost due to the myopathic process are replaced by non-elastic fibrous tissue resulting in a loss of muscle elongation. As a result, the shortened/shrinking muscle reduces the extention of the joint on which it acts. For example, a fibrous biceps muscle prevents full extension of the elbow (it no longer elongates sufficiently) and the result is an elbow in flexion. Therefore, in myopathies we speak of fibrous retraction or contracture to indicate this situation.
Rigidity (Parkinsonian) and spasticity (e.g. stroke), on the other hand, are contractions originating from alterations in the nervous system and can be reduced by muscle relaxants used during anaesthesia. Myopathic fibrosis, on the other hand, is a mechanical shortening phenomenon that clearly cannot be reduced by drugs.
On the subject of tendon retractions, which are more than just simple contractures, surgery is sometimes recommended to lengthen the tendons and allow ample limb movements. Can you shed some light on this as well?
Tendon retractions are treatable, but it is important to identify the ideal timing, when the retraction is still elastic. To maintain the ability to ambulate, mild retraction can be counteracted with the use of a walking support, which is minimally invasive and easy to use. The brace should be used as long as it can maintain the foot in a physiological 90° position. For example, if the foot is in an equine position and rests on the toes, the patient will have unstable balance. The use of night supports can be helpful, but if the retraction exceeds the force of the brace, a minimally invasive procedure can be opted for in order to lengthen the Achilles tendon, or, in the case of internal rotation of the foot (known as ‘varus’ or ‘supinated’), other tendons can be lengthened. These procedures are generally quick and require immobilisation with a plaster cast for about a month. This allows the tendons to be lengthened or the patient to walk again. The same reasoning applies to the knee.
Other times, however, it is not taken into consideration by the doctors themselves because it would have to be repeated over and over again and is not conclusive for those with degenerative diseases, like us.
That’s not quite correct, Giulia. I step in when the muscular imbalance has caused clubfoot. I correct the tendon, but I cannot stop the progression of the disease. I balance the strength in the position where I have operated, but it is the disease itself that continues to progress. This is the great variability. I have operated by lengthening tendons in patients who, 10 or 12 years after surgery, are still able to walk with just a slight progression of the disease, but are extremely satisfied with one single operation. Other patients, on the other hand, required up to three operations in five years because the disease was progressing and the deformity continued to worsen, resulting in them losing the ability to walk in the meantime. When faced with a retracted condition that affects the ability to stand upright, what can I do? Stretch the tendons again.
And without surgery, what can be done? A girl member, suffering from Ullrich dystrophy in an electronic chair with CPAP therapy, told me that she had suffered a compound fracture of the femur. The solution she adopted, thanks to Dr Merlini and his invaluable advice, was to avoid surgery and proceed with immobilisation with a knee brace. Today the girl is in good health. What are the risks in such cases that tend towards avoiding surgery?
When a bone breaks, it heals naturally with the formation of a bone callus. During this period, there is often a lot of pain and, for over 250 years, splints have been used to reposition the bone. In the last 100 years, certain particular fractures, such as those near joints or those requiring more complex healing, are stabilised with metal plates, screws or nails. The nail acts as a support for the bone pieces until a solid union is formed. The procedure can be compared to a carpenter’s clamp holding two pieces of wood together until the glue has dried. However, if we consider a non-ambulatory patient who suffers a fracture and we are able to align the bone and manage pain effectively without surgery, what is the advantage of surgery? In this case, the risks associated with the operation outweigh the benefits. On the other hand, if the patient is still able to walk, surgery may be preferable to enable him or her to get back on their feet as quickly as possible.
Can you explain the link between bone weakness with basic muscle weakness? How can we intervene to prevent fractures or possible bone weakness?
I suggest you talk to Prof Merlini. I am a carpenter!
Dr Merlini, tell us more. Can you please answer the question?
‘Bone weakness’ is a consequence of muscle weakness and immobility. One must therefore consider two main types of fractures: those caused by a fall and those due to osteoporosis. In patients with Bethlem myopathy, moderate muscle weakness is an important risk factor for falls and subsequent fractures. In order to prevent falls, the sufferer must avoid overexerting his or her muscles and stop when he or she starts to get tired.
Patients with increased muscle weakness have poor mobility. Immobility in turn can lead to loss of bone mineral component and subsequent osteoporosis, which further increases the risk of fractures. It should be borne in mind that osteoporotic fractures occur spontaneously or with minimal effort and mainly affect the vertebral bodies, the neck of the femur, the upper arm and forearm near the wrist. Patients in wheelchairs must be secured with a belt. These patients must be lifted and moved with great care, especially when help is given by persons outside the family.
We read that your father founded Orthopaedics, a small voluntary association that travels to developing countries to operate on patients, mostly children, with orthopaedic conditions.
Ever since my formative years, I have had a keen interest in voluntary work, an interest I have never lost. In 1993, I took part in a trip to Peru with a group of young people studying infectious diseases and decided to replicate the experience in the orthopaedic field. In 1989, I went on a trip to Tanzania with my father, also an orthopaedist, where we adopted a small hospital that cared for children with orthopaedic conditions, including muscular dystrophies. Since then, I have never stopped dedicating myself to these missions. Next 29 April, I will be leaving for Cameroon, where we helped found a hospital. It will be an extraordinary experience, because after 20 years of collaboration, we will be witnessing the construction of an orthopaedic pavilion, which we will inaugurate together. I invite all your members to follow our social channels, where we will share real-time updates on the mission and the work we will be carrying out. The expedition will involve 12 doctors, technicians and physiotherapists and will last 7 to 10 days, during which we will operate on about 50 to 60 children and adults. Afterwards, we will leave the patients in the care of our local colleagues in Douala. Sharing these experiences on social media is an important way of raising awareness and getting everyone involved.
As an orthopaedist on our medical-scientific committee (I don’t know if you knew this, but by accepting this interview you consented to your appointment to the MSC of the Collagen VI Association). Would you like to say something about this?
Thank you. I accept this with pleasure.
You are of course invited to the meeting in Bologna that we will organise with Merlini. You will come to the next meeting, won’t you?
Thank you very much. I’ll do my very best to be there. Patient associations nowadays are fundamental. The only serious approach in the field of rare diseases is to create a system. Create a core of experience. All together.
Dr Cesare Faldini cesare.faldini@ior.it, Dr Luciano Merlini mrllcn@unife.it.