The Rizzoli Orthopedic Institute in Bologna enjoys a prestigious national reputation. Dealing with rare neuromuscular pathologies complicates the approach, as in any specialized field. However, Cesare Faldini, a well-known figure to many of us, stands out for his determination and expertise, particularly evident in his ongoing orthopedic studies related to muscular dystrophies. The purpose of this interview is to explore his character for our members and readers.
We’ve already touched on your role at the IOR as an orthopedic surgeon, professor, and researcher, but would you like to further describe yourself?
I’m Cesare Faldini, and I work as the Director of Orthopedic and Traumatological Clinic 1 at the Rizzoli Orthopedic Institute, affiliated with the University of Bologna. My connection with Luciano Merlini dates back to the time of my orthopedic thesis. Subsequently, upon completing my studies, I joined Rizzoli, where I had the opportunity to collaborate with this extraordinary researcher. Merlini is a unique personality who has turned orthopedic challenges into opportunities for studying neuromuscular diseases. Until the 1950s-60s, neurologists focused on other pathologies within major neurological institutes, such as strokes and Parkinson’s disease. Merlini, being immersed in an orthopedic environment at Rizzoli, directed his attention to neurological diseases with orthopedic consequences, turning what was seen as a limitation into an opportunity. His experience is considered unique worldwide and is admired by scholars around the globe.
The Rizzoli Orthopedic Institute, founded in 1896, was the world’s first to separate orthopedics from general surgery, an initiative that helped establish Bologna as the cradle of orthopedic surgery. In 1905, the British Orthopaedic Society was founded in Bologna, recognizing the pioneering role of the Institute. This allowed Rizzoli to attract patients with orthopedic deformities resulting from various pathologies for over 125 years, solidifying its reputation nationally and internationally. Professor Merlini has fully exploited this unique resource in the world, turning challenges into unprecedented study opportunities.
In the 1990s, I had the honor of joining Rizzoli while Merlini was already active in his role. Thanks to his extraordinary case studies and my passion for research, I asked to collaborate with him. My mentor, Professor Sandro Giannini, former Director of Orthopedic Clinic 1, told me that Merlini would enrich my knowledge, being himself a true scientist in the medical field. But what do medical scientists do? Medical scientists, with great humility, carefully observe patients and derive treatment rules from their common characteristics. Every observation-based process requires humility, as observation is the key to learning. Collaborating with Dr. Merlini, I learned to observe carefully. Our collaboration was fruitful: Merlini contributed his expertise in diagnosis, while I developed my skills in surgery. Together, we achieved extraordinary results, combining our knowledge in a synergistic blend.
So before your encounter with Merlini, what had you dealt with regarding neuromuscular pathologies?
Before my encounter with Merlini, my experience with neuromuscular pathologies was limited. Muscular dystrophies, while sporadic, are a consistent presence in orthopedic clinics. However, their rarity poses a significant challenge. Without a specialized center and a steady stream of cases, developing thorough expertise proves particularly complex. As you can imagine, for instance, every two years a patient with a specific issue may arrive, and while the doctor observes them, providing a precise diagnosis may be challenging due to limited experience. The key has been to establish a system and gather a multitude of cases. Each patient contributes to the solution, generating valuable insights not only for their own treatment but also for future patients.
Another ongoing study is the “3D Modeling of Muscle-Tendon Units to Identify Tissue Interaction in Muscular Dystrophies and Aging (3D-MTU)” by Vittoria Cenni and Patrizia Sabatelli from the CNR in Bologna, collaborating with Paolo Bonaldo’s team from the University of Padua. What is your role?
Our collaboration with Dr. Merlini has enabled us to secure funding for projects and to contribute to the genetic characterization of Ullrich muscular dystrophy, focusing on autophagic issues and alteration of collagen VI. At our center, we collect muscle and adipose tissue samples from patients and send them to laboratories. This project has led to the creation of an expertise field that, with pride, I describe as unique worldwide. We have secured funding for 4 projects from the Ministry of University and Research, which have contributed to the genetic characterization of this severe condition. My collaborative relationship with Dr. Merlini has also been enhanced through collaboration with Prof. Paolo Bonaldo of the University of Padua, who is an internationally renowned expert on Collagen VI (read the interview with Paolo Bonaldo, click here).
This collaboration has allowed us to win projects and to contribute to the genetic typing of the entire genetic part of Ullrich muscular dystrophy, focusing on autophagic issues and alteration of collagen VI. Our team at Rizzoli takes muscle and fat tissue samples from our patients, and by sending them to laboratories, we have followed the process and matched the clinical condition we see with the exceptional observations of Prof. Bonaldo and neurological considerations of Prof. Merlini. This has resulted in an expertise field that I proudly describe as unique in the world. We have won 4 projects from the Ministry of University and Research with which we have contributed to typing the genetics of this severe condition (To read the explanation of this study project, read the interview with Dr. Vittoria Cenni, click here).
It is known that you have written a monograph on degenerative scoliosis. One of the effects of collagen VI deficiency disorders is the appearance of scoliosis, which is inevitably degenerative. Could you please give us a brief explanatory explanation of the difference between idiopathic and neuromuscular scoliosis?
Scoliosis means that the spine, when viewed from the front, perfectly straight, begins to curve. It is a very complex condition with many origins. In most cases, the cause is unknown, and in this case, we are talking about idiopathic scoliosis, where scoliosis typically begins to curve with the onset of growth and stops when growth ends. By intuition, the earlier it appears, the more severe it is. If it appears only a year before growth ends, it will remain of a few degrees, but if it appears at age 6, it can worsen during the long growth period. Scoliosis worsens with the rule of doubling, meaning that each year, if left untreated, it doubles. The first doublings are not concerning because below 10 degrees, scoliosis is non-existent, so defining a curve below 10 degrees as scoliosis is a mistake. The Almighty did not use a protractor when He made us. From 10 to 20 degrees are mild forms that do not require treatment. Treatment begins from 20 degrees onwards. From 20 to 40 degrees, they are treated. Beyond 40 degrees, they are severe. Then there is the opportunity for surgery. In short, the first doublings are harmless, going from 2 to 4 and then to 8. In the early years of scoliosis, nothing happens. The problem is that it then goes from 8 to 16 and then to 32. The next doubling brings us into the need for surgery. Within 5 doublings, the entire scoliosis occurs. It is clear that medicine must intercept a patient and only observe them when they have scoliosis below 16 degrees and then treat them so that it does not go from 16 to 32. Then, if it goes from 32 to 64 or beyond, surgery must be considered. This is the role of prevention, control, and medicine.
This same rule also applies in neuromuscular diseases with some differences. In neuromuscular disease, there is an imbalance of forces, and therefore, some muscles on one side pull more than the other, so there is a known efficient cause. Neuromuscular disease acts from birth, and scoliosis can become very severe, mainly because if muscular dystrophy does not produce the imbalance, the spine remains straight. However, as you well know, not all muscles are affected in the same way, order, and extent. When the muscle is affected by dystrophy, the rule is that the worsening occurs much more rapidly than in idiopathic scoliosis. When this asymmetry appears, the curve progresses very quickly.
Moreover, since we are talking about long muscles, they also include the pelvis, that is, the pelvis. In neuromuscular scoliosis, the pelvis behaves as if it were a vertebra, and it also rotates along with the spine, which is a big mess! The imbalance of the pelvis makes it difficult to sit, and if the pelvis tilts, one leg appears longer and one shorter, and for a patient sitting down, sitting on one buttock is uncomfortable, and there is a need for a brace, a lateral support given the inclination/imbalance. These conditions are obviously the specific differences between idiopathic and neuromuscular scoliosis. Another characteristic of neuromuscular scoliosis is that if it is intercepted when it starts to double, it is very elastic, even more elastic than idiopathic scoliosis, so the force to straighten it is much lower even at the surgical level. There is this “golden time” when scoliosis begins and the patient is already sitting in a chair and feels it starting to lean to one side. Bringing it back straight with a surgical act is less burdensome. If I leave it as it is, it will stiffen over time, and the surgery will become more challenging.
So no neuromuscular scoliosis remains elastic?
Initially, all neuromuscular scoliosis present a certain degree of elasticity, but over time, they all tend to stiffen. It is an intrinsic characteristic of human evolution.
We know that wearing a brace is recommended, which is sometimes called corrective and sometimes maintenance. I suppose in our cases, it is mostly maintenance, or am I wrong? Does it depend on the type of scoliosis, medical history, and materials involved? Can you clarify this a bit?
The brace is corrective. If I intercept a child with 16 degrees of scoliosis and put a brace on them, and if in that year it remains at 16 degrees, how much have I corrected it? 16 degrees because it should have reached 32 according to the doubling rule, but it didn’t! This is called correction! In all scoliosis, the brace is applied to interrupt this chain that continues according to the power of two because remember, when I put a brace on a child with 4 years of growth, we remember the doubling: 16, 32, 64, 128! We cannot leave it to itself. It’s dangerous! If in 4 years of wearing the brace, I have only doubled from 16 to 32, I will have gained 96 degrees of correction. The ideal brace worn for an ideal period stops the worsening.
The point is that nobody stays in a brace 24 hours a day. We know that brace treatment slows the progression of scoliosis depending on the patient’s shape, respiratory capacity, their cooperation, the family’s support and motivation; there are many parameters that make a brace wearable. The brace is an opportunity, but it must be tailored to the patient. No blame should be placed. There is a force of worsening that varies from patient to patient and depends on their ability to wear it. Ideally, the curve stops and does not double. Of course, it is easier to intervene during puberty when there is no worsening force from the neuromuscular pathology, and the muscles are imbalanced. It must be said that the brace is not always an opportunity because if I have a patient who is still walking but has little strength, balance issues, and maybe a reduced rib cage size. If I were to put on the brace, they would lose the ability to walk due to the added weight. Here the choice is brace or surgery? The scoliosis that would progress without the brace would cause problems such as a twisted pelvis, chest closure, etc. The choice is difficult, but the stakes are high.
When a neuromuscular patient wears a brace, do they lose strength in their chest muscles? Do they become dependent on the brace to the point where they can’t even take it off at the beach?
When a patient with a neuromuscular condition wears a brace, they do not necessarily lose strength in the chest muscles. The purpose of the brace is to prevent the deformation of the spine by the muscles that are not yet compromised. In the context of neuromuscular diseases, it is muscle weakness that causes the curvature of the spine, and the brace intervenes to counteract this imbalance. In theory, if both muscles were paralyzed, scoliosis would not occur. However, reality is more complex because muscles tend to weaken unevenly. Therefore, not all patients can tolerate wearing the brace, and each has a unique medical history. It is important to avoid extreme approaches, such as saying “brace or death,” as not everyone is suitable for this solution, just as it is wrong to categorically state “I will never wear it,” considering that surgery presents other complications. Caution is necessary. Keep an eye out.
Dr. Merlini, could you kindly respond to the same question?
The loss of strength in the muscles supporting the back, which leads to scoliosis, depends on the underlying disease. It has never been scientifically proven that wearing a brace leads to a decrease in muscle strength for this reason. The function of the brace in muscular scoliosis is twofold: to allow a more comfortable sitting position and to reduce the progression of the scoliotic curvature.
The first goal is achievable and often can be maintained for a long time. It is the solution in cases where surgery is too risky or when the optimal time has passed. The tolerability of the brace in these cases depends on various factors, not least of which is how well it is made. Let’s not forget that the brace is a manufactured product, and the quality of the craftsmanship, especially in difficult cases, makes a difference. So, while it cannot be generalized, it can be safely said that a good brace can be a good solution in certain cases to achieve a comfortable sitting position. Unlike surgical intervention, which corrects scoliosis definitively, the brace corrects the scoliotic curve only when worn. Once the brace is removed, the scoliosis returns to its initial state. Therefore, it can be said that the brace “masks” but does not correct scoliosis. The notion that the brace then reduces the progression of muscular scoliosis is like saying that it strengthens spinal muscles, and this too is a statement that lacks scientific evidence.
How much do physical activity and physiotherapy impact?
From the perspective of the curvature angle, no physical activity has been shown to influence scoliosis progression. However, physical activity is crucial for overall well-being. Good muscle tone improves physical endurance and mobility. Physiotherapy, combined with muscle strengthening, is essential for maintaining residual muscle function and improving respiratory capacity. Additionally, physiotherapy helps to balance the body and improve posture. Although it doesn’t directly affect the scoliosis angle, it significantly contributes to the patient’s overall well-being. It creates balancing and static exercises but has no effect on the scoliosis angle.
In the case of severe curves, the commonly performed procedure is selective corrective spinal arthrodesis using pedicle screws and titanium rods. What does it consist of?
The corrective arthrodesis procedure has completely changed because when I started my work as an orthopedic surgeon and collaborated with Merlini, operating on scoliosis required applying hooks to the vertebrae, with one at the top and one at the bottom of the spine, connected by steel rods pulling on them. This meant that the pulling force was minimal, and for about 3 or 6 months, a patient could technically disengage the hook from the vertebra with a sudden movement and require surgery again. Today, thanks to advances in technique, titanium rods connected to each vertebra by screws can perfectly straighten the spine.
This procedure works so well when the curve is intercepted in the elastic phase, and although we now have tools to correct even rigid scoliosis, the stiffer the spine, the more aggressive we need to be in the operating room. Neuromuscular patients are delicate, so the lighter the touch, the fewer complications. To correct rigid curves, a slice of the vertebra needs to be removed, and you can imagine that this vertebra removal procedure was pioneered by us worldwide. It’s performed by only a few centers because it’s extremely risky, requiring signing a consent form with very high risks. The average duration is 10 hours, with a need for transfusion every hour. Prolonged awakening in intensive care for 2 or 3 days after the procedure. It’s the last resort for those who let the curve progress too far into rigidity. Surgeons are committed to addressing a problem, and you can imagine the compromise of internal organs due to the compressed curve.
This procedure has a mortality rate, and mortality is not due to incompetence, negligence, or poor commitment of the treating physician. We have always had successful outcomes, but other centers report a mortality rate of 5%. The fact that we have never experienced it doesn’t mean the risk isn’t there. It’s a decision that must be made consciously, without catastrophizing but with realism. It’s the most complicated surgery in general. Our anesthesiologists have compared it, from an anesthesiological point of view, to liver transplantation.
Have there been cases where the surgery was impracticable due to reasons unrelated to the patient’s will?
One cannot generalize. There is no universal answer to this question. Each patient follows a unique path and brings their own medical challenges. When it comes to scoliosis issues, it’s essential to seek out a specialized center where a competent team works together to assess each individual case. In our center, for example, the contribution of Dr. Merlini, even though retired, remains crucial due to his extensive experience and knowledge. The decision regarding surgery depends on the overall evaluation of the team: if the scoliosis is elastic, the surgery may take less time (for example, 4 hours), whereas if it’s partially elastic, it might be longer (6-7 hours). However, in cases of severely advanced scoliosis where parts of the vertebrae need to be removed, this entails significant risks that other centers might avoid. We are the only center performing this because this surgery carries a risk coefficient that others are not willing to tackle. When the risks outweigh the potential benefits, our team may decide that surgery is not the best option for the patient.
A girl among us who helped me prepare the questions told me she underwent the surgery. She experienced complications during intubation but was satisfied with the surgery for about three years. Then, problems gradually started. First, hip pain, then back pain recently. The surgery went well, and the rods are still in place, yet the vertebrae continued not to bend, increasing the degrees but to rotate. She was advised to have joint injections to combat the pain. What do you think about injections in non-idiopathic cases?
I don’t know. It’s such a complex clinical condition where the patient needs to be thoroughly studied to find the solution. The way out. We’re talking about an extremely personalized condition that can’t be generalized. Usually, those who perform such interventions have extensive expertise. Turn to your treating physician and let them find a solution for you.
Do you want to talk about any class of muscle relaxants that can reduce stiffness, even if not targeted specifically for those with Collagen VI deficiency without addressing the root of the problem? Can a muscle relaxant actually help, or are there side effects that would become significant in our cases?
I suggest speaking with Professor Merlini. I’m a carpenter.
Dr. Merlini, could you kindly answer the question?
In myopathies, muscle fibers lost due to the myopathic process are replaced by inelastic fibrous tissue, resulting in a loss of muscle lengthening. Consequently, the shortened/retracted muscle reduces the range of motion of the joint it acts upon. For example, a fibrotic biceps muscle prevents full extension of the elbow (it no longer stretches sufficiently), resulting in a flexed elbow. Therefore, in myopathies, the terms fibrotic retraction or contracture are used to indicate this situation. Rigidity (as in Parkinson’s disease) and spasticity (as in stroke, for example) are contractions caused by alterations in the nervous system and can be reduced by muscle relaxants used during anesthesia. Myopathic fibrosis, on the other hand, is a mechanical phenomenon of shortening that cannot be reduced with medication.
Regarding tendon retractions, which are not just simple contractures, sometimes surgery is recommended to lengthen the tendons and allow for greater movement of the limbs. Can you clarify this as well?
Tendon retractions are treatable, but it’s important to identify the ideal timing when the retraction is still elastic. To maintain the ability to walk, a mild retraction can be countered with the use of a brace, which is minimally invasive and easy to use. The brace should be employed as long as it can keep the foot in a physiological position at 90°. For example, if the foot is in equinus position and resting on the toes, the patient will have an unstable balance. The use of night splints may be helpful, but if the retraction exceeds the strength of the brace, a minimally invasive procedure to lengthen the Achilles tendon can be considered, or in the case of internal rotation of the foot (called “varus” or “supinated”), other tendons can be lengthened. These procedures are generally quick and require immobilization with a cast for about a month. This allows for tendon elongation or enables the patient to resume walking. The same reasoning applies to the knee.
Other times, however, it’s not considered by the doctors themselves because it would need to be repeated multiple times and is not conclusive for those with degenerative conditions like us.
It’s not quite like that, Giulia. I intervene when muscle imbalance has caused equinus foot. I correct the tendon, but I don’t halt the progression of the disease. I balance the strength in the position where I operated, but it’s the disease itself that continues to progress. This is the great variability. I’ve operated on patients by lengthening the tendons, and even after 10 or 12 years post-surgery, they’re still able to walk with a slight progression of the disease, but they’re extremely satisfied with a single intervention. Other patients, however, have required up to three surgeries in five years because the disease was progressing and the deformity continued to worsen, leading to loss of the ability to walk in the meantime. When we’re faced with a retraction condition that threatens the ability to stand upright, what can I do? I lengthen the tendons again.
And without surgery, what can be done? A member affected by Ullrich congenital muscular dystrophy, who uses an electric wheelchair and CPAP therapy, told me about having sustained a compound femoral fracture. The solution, thanks to Dr. Merlini and your invaluable consultation, was to avoid surgery and proceed with immobilization using a knee brace. Today, the young woman is doing well. What are the risks in these cases that lead to avoiding surgery?
When a bone breaks, it naturally heals with the formation of callus bone. During this period, there is often significant pain, and for over 250 years, splinting has been used to realign the bone. In the last 100 years, some specific fractures, such as those near the joints or those requiring more complex healing, have been stabilized with metal plates, screws, or nails. The nail serves as support for the bone pieces until a solid union is formed. The surgery can be likened to a carpenter’s clamp holding two pieces of wood together until the glue dries. However, if we consider a non-ambulatory patient who suffers a fracture and we are able to align the bone and effectively manage the pain without surgery, what is the benefit of surgery? In this case, the risks associated with surgery outweigh the benefits. On the other hand, if the patient is still able to walk, surgery may be preferable to enable them to stand up as quickly as possible.
Can you explain the connection in these cases between bone weakness and underlying muscle weakness? How to intervene to prevent fractures or potential bone weakness?
I invite you to speak with Prof. Merlini. I’m just a carpenter.
Dr. Merlini, could you kindly answer the question?
“Bone weakness” is a consequence of muscle weakness and immobility. Therefore, two main types of fractures should be considered: those from falls and those from osteoporosis. In patients with Bethlem myopathy, moderate muscle weakness is an important risk factor for falls and subsequent fractures. For fall prevention, individuals with myopathy should avoid overexerting their muscles and stop when they begin to feel tired.
Patients with greater muscle weakness have poor mobility. Immobility, in turn, can lead to loss of bone mineral content and subsequent osteoporosis, which further increases the risk of fractures. It is important to note that osteoporotic fractures occur spontaneously or with minimal effort and mainly affect the vertebral bodies, the neck of the femur, and the upper arm and forearm near the wrist. Patients in wheelchairs should be secured with seat belts. These patients should be lifted and moved with great care, especially when assistance is provided by individuals outside the family circle.
We read that your father founded Orthopaedics, a small volunteer association that travels to developing countries to operate on patients, mainly children, with orthopedic conditions. Can you tell us more about it?
Since my training days, I have had a strong interest in volunteering, a commitment I have never lost. In 1993, I participated in a trip to Peru with a group of young people studying infectious diseases, and I decided to replicate the experience in the orthopedic field. In 1989, I traveled to Tanzania with my father, also an orthopedist, where we adopted a small hospital that cared for children with orthopedic conditions, including muscular dystrophies. Since then, I have never stopped dedicating myself to these missions. On April 29th, I will leave for Cameroon, where we have helped establish a hospital. It will be an extraordinary experience because after 20 years of collaboration, we will see the construction of an orthopedic pavilion that 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 do. The expedition will involve 12 doctors, technicians, and physiotherapists and will last 7 to 10 days, during which we will operate on about 50 or 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 to raise awareness and engage everyone.
As an orthopedic specialist of our medical-scientific committee (I don’t know if you were aware, but by accepting this interview, you have consented to your appointment to the CMS of the Collagen VI association). Would you like to say something about it?
Thank you. I gladly accept.
You are, of course, invited to the gathering in Bologna that we will organize. Will you come to the next gathering, right?
Thank you very much. I will do my best to be there. Patient associations are crucial nowadays. The only serious response in the field of rare diseases is to create a system. To build a core of experience. All together.