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SA: Hello and welcome to Master the MRPCH. In this series, we tap into the expertise here at Great Ormond Street Hospital to give you an overview of a topic on the RC PCH exam curriculum. So whether you're revising for an exam or just brushing up on a need to know topic, hopefully this podcast can give you the information that you need.
I'm Dr. Sarah Ahmed, a pediatric registrar and the current digital learning education fellow here at GOSH. Today we are very lucky to have back, friend of the show, Dr. Maria Gogou, a senior clinical fellow in paediatric neurology. She's going to be talking about an approach to the floppy baby which maps to learning outcomes in the Neonatology and Neurology sections of the exam curriculum.
Maria, thank you for joining me today.
MG: Hello, Sarah. Thank you for being here.
SA: So before we delve into more detail, I wanted to start by asking, what would you like people to get out of this podcast?
MG: Well, I would like people listening to this podcast to be able to adopt a systematic approach when they deal with a floppy baby, an approach which is mainly guided and based on findings from clinical examination and information from medical history. And also, I would like them to be able to avoid some common pitfalls in everyday clinical practice.
SA: I think those are really worthwhile learning outcomes and hopefully we'll cover everything today. So, let's dive in.
What do we mean, Maria, when we talk about floppiness?
MG: Hmm. This is really a very, very good question. Because sometimes people mean different things with the word floppiness. The medical word for floppiness is hypotonia. So floppiness refers to low muscle tone. And what does this mean in clinical practice? It refers to this lack of the ability to sustain the postural control. Or in other words, it refers to this reduced resistance when doing a passive range of movements around the joints.
Many people, when they use the word floppiness, they refer to weakness. So they suggest a weak baby. However, this is not always the case. What actually happens is that a baby who is weak is usually floppy as well. So they usually have low muscle tone. However, the opposite is not always true. So we may have a baby with low muscle tone, but actually being quite active and strong.
SA: I see, I don't think I quite realize that differentiation that you've made really clear there.
So, talking about approaching the floppy baby, are these patients that we see quite commonly?
MG: Yes, this is a quite common problem in our everyday practice. It is very hard, I would say almost impossible, to say how frequent it is because hypotonia is actually a symptom rather than a diagnosis, and there are a number of different causes may be behind this symptom. However, a paediatrician, a paediatric neurologist, or a neonatologist may need to assess an infant with floppiness under many different circumstances, like, in intensive care unit, in a ward, as a telephone consultation, or in the outpatient clinic.
SA: I really liked how you said there that floppiness is a symptom as opposed to a diagnosis. I'm guessing that there are lots of causes for floppiness. Can we talk about a few of them?
MG: Exactly, the differential diagnosis is really very, very broad. There's a huge list of potential causes. I think the most sensible thing is to be aware that we have central and peripheral causes of hypotonia, of floppiness. And when I say central, I mean causes which involve central nervous system. Whereas peripheral causes mainly refer to the peripheral parts of the nervous system, which means the anterior horn cells, the nerves, the neuromuscular junction, or the muscles themselves.
Now, if we speak a bit more about the central causes of floppiness we can think about cerebral malformations, chromosomal disorders, inborn errors of metabolism, which affect as well the central nervous system, hypoxic ischemic encephalopathy.
Whereas in the second case, in the case of peripheral hypotonia, we must have in mind the cases of spinal muscular atrophy. We must have in mind cases of congenital myasthenia or congenital myasthenic syndromes.
We need to be aware of some acquired causes of floppiness like infantile botulism and also diseases which affect the muscles like congenital myopathies or congenital muscular dystrophy or myotonic dystrophy.
And of course we need to have in our mind that there might be some overlap in some cases. So, there are babies who can have involvement both from central and peripheral nervous system, like what happens in a number of metabolic disorders or in a number of chromosomal syndromes, as well as some systematic causes of floppiness, like a sepsis, an infection or like hypothyroidism, for instance.
SA: That's such a wide range of differential diagnosis that, for me at least, it can seem a little bit overwhelming. How do you go about approaching a floppy baby from a diagnostic point of view?
MG: I would say that the cornerstones are clinical examination and a very detailed history, both personal and family history. It's important to get a history from prenatal period from gestation and ask questions about any use of medications. Any anatomical problems that mum could have. Also about birth conditions and investigate about the occurrence of any events which could predispose to hypoxic ischemic injury. It's important to ask about family history of any neuromuscular disorders, for instance. And to clarify if there is any case of parents being relatives, as this increases the risk of some inherited disorders.
It is also important when we take the medical history to ask about the progress of this symptom. So it is very important to clarify if floppiness is static, if it's getting better with time or if it's progressive and getting worse. And it's also important to clarify if this has been a chronic problem, which has been present since the birth, or it happened acutely. For example, in the case of infantile botulism, we usually expect symptoms to occur suddenly, we need to investigate the consumption of any honey products, which could predispose to that. On the other hand when we have a neuromuscular condition, we expect to see signs and symptoms from the very early of life, and those to have a static or progressive sometimes course. And of course, we may not forget that there are sometimes cases of benign infantile floppiness which can be related to a family history with a similar developmental course in one or both of parents. So in that case, we will see an improvement with time. And also in those cases individuals and their families frequently have excessive joint laxity.
SA: We’ve spoken a lot about the history, could you talk us through performing a clinical examination?
MG: Yes, as I said before, floppiness and weakness are two different things. When we examine a floppy baby, it's important to find out whether there is coexisting weakness or not. Floppiness, as I said, refers to this reduced resistance when we passively try to stretch muscles around the joints. In order to do this in clinical practice, it's important to try and stabilize the joint we examine. For instance, when we want to flex and extend elbow, we need to hold stable the arm. When we want to flex and extend the wrist, we need to hold stable the forearm and so on. On the contrary, in order to assess weakness, whether weakness is present it's important to observe the spontaneous anti-gravity movements of the baby. If we do not see them, we need to make sure the baby is awake or offer some tactile stimuli. Of course, this may take some time because we may be called to assess a baby who is intubated and also has been given muscular relaxants. So in that case, we need to assess the baby again and again. It is important to differentiate between anti gravity movements and horizontal movements of the limbs because what we focus on to assess weakness is the anti gravity movements. And also we can gain useful information from looking at the intensity of the cry of the baby, facial expressions, at eye movements, at some neonatal reflexes like the sucking reflex and the moro reflex, how prominent they are. And also to look at the respiratory function of the baby, because this can also be suggestive of an underlying weakness or not. So this is a very important thing.
Another important thing during clinical examination is to check whether floppiness appears to be central or peripheral. And the very useful clue for that is to check the deep tendon reflexes. So in the cases of a central cause of floppiness, we will have preserved reflexes or even brisk and prominent sometimes. On the other hand, in the case of a peripheral of floppiness of a peripheral cause the reflexes will be diminished or sometimes even absent.
I would like to highlight that sometimes babies who are found to be hypotonic in the beginning of their life, they may develop spasticity later in their life. And this usually happens in the case of a central cause of floppiness, like if we have a background of hypoxic ischemic injury. So useful clues in this case would be some strange posturing of these babies. For example, they can have a tight fisting of their hands with their thumbs enclosed by the rest of fingers, or they may have a poor repertoire of their movements or some scissoring of their legs. So those are useful clues, which also help us talk about prognosis in future. In the case of central floppiness, we will also have other symptoms from central nervous system. For instance we may have seizures, we usually have a baby who looks encephalopathic or having coexisting apnoeas as well. It is important to look for dysmorphic or distinctive facial features, which could point towards a specific diagnosis of a genetic syndrome. And another important clue is to look for contractures. In some cases of neuromuscular disorders, we can have contractures of the joints present even from the beginning of life. And this is suggestive of poor movements during gestation. And it's also very, very important to look at the feeding and respiratory function of those babies. Feeding and respiratory difficulties are very frequent in a number of babies with floppiness, especially in those with neuromuscular disorders, and also need urgent and prompt treatment.
And another important thing I would like to highlight is that in the cases of peripheral floppiness, especially when the underlying cause is spinal muscular atrophy, we will expect to see a quite floppy baby with a very typical frog legged posture. But characteristically, those babies will have normal eye movements. They look quite alert and looking around them with interest in the environment. And they may typically have some tongue fasciculations as well.
SA: Just thinking about the other aspects of the neurology exam, do you ever get associated changes in sensation? Or is it usually all motor related?
MG: In the cases we have weakness because of a nerve problem, sensation disorders are also expected. For instance in cases of Charcot Marie Tooth, we will have also sensation being affected. This is not always easy to assess in infantile period. And regarding other causes which are more prominent in this age group, like spinal muscular atrophy, or congenital myopathies, myotonic dystrophy, or muscular dystrophy, we don't expect to see them as a prominent finding.
And I forgot to mention before that it's also important sometimes to examine the parents of the child. For example there are cases of family history of congenital myotonic dystrophy. And when we examine the mother of the child, we can find the findings of myotonia. For example, we can ask her to squeeze the examiner's fingers or close her eyes tightly and then has some delay with the relaxation of muscles. This is a very important clue because actually it suggests diagnosis in the newborn child as well. Or we might ask a mom for symptoms of myasthenia. In a number of cases parents are even unaware of the diagnosis in themselves and get diagnosed once we have made diagnosis for their child, because you know, symptoms sometimes tend to be worse in future generations.
SA: So really what you're doing is you're using your history and your exam to try and narrow down whether or not you think this is central or peripheral and then going from there.
MG: Exactly, because if we have a good idea, if there is a central or a peripheral cause, this can narrow significantly the investigations we would request for this baby. For example, if we have strong suspicion about the central cause, then it's very important to get neuroimaging as soon as possible, an MRI scan, for example, and also initiate some investigations, including genetic tests or metabolic tests.
On the other hand, if we have a strong flavour of a peripheral cause of floppiness then the first and most important and easiest investigation we can do is to measure CK level in blood. And in case we find a high CK level, this points mainly toward a muscle disease like congenital muscular dystrophy or congenital myopathy.
In the case we find a normal CK, this would be more consistent with other conditions like spinal muscular atrophy or congenital myasthenic syndromes, for instance. To be honest, nowadays, and because there is a very huge progress in the field of treatment of neuromuscular disorders, and there are available genetic treatments for spinal muscular atrophy, if we have a floppy newborn or small infant and suspect SMA 1, it is important, no matter the level of CK, to request targeted genetic testing of the spinal muscular atrophy gene in order to diagnose this condition as soon as possible and start treatment as soon as possible, as this will change the natural course of this disease.
And also regarding investigations, we have additionally the tool of nerve conduction tests and also the muscle biopsy. Nerve conduction tests can be very useful and give us information which differentiate from a muscular cause between the muscular cause and the cause affecting the neuromuscular junction the nerves.
It is important that when we suspect a congenital myasthenia to request a single fibre electromyograph as well, which is the right test in order to diagnose this condition. And of course, muscular biopsy can be revealing in a number of cases, although nowadays with a prominent use of genetic tests and the quite significant increase in the speed the results get available, the need for those tests is not so high as it used to be years ago
SA: Are there any caveats to what we've spoken about? Any kind of special tips that you need to keep in mind?
MG: Yes, an important caveat is the levels of CK. So as I said before, we expect CK to be high in cases of myopathy or muscular dystrophy. However, we need to have in our mind that in babies who have been born with normal vaginal delivery the levels of CK can be quite high, up to 10 times higher than normal for the first week of their life. So we need to have that in mind when we measure CK in a newborn, that it might be falsely elevated. And for the same reason, if we find a high level of CK in a baby in the first week of life, especially if there was a quite difficult and vigorous labour, this does not necessarily exclude other conditions like SMA or congenital myasthenia, for example. So this is something we need to have in our mind.
And another important caveat, is that sometimes as I said, we get many referrals and calls to assess babies with floppiness. It is a mistake to ask for investigations before we examine the baby. Because sometimes information given by a third person might be different from what we see when we examine the infant. And this can actually help us avoid unnecessary investigations, which sometimes can increase stress and anxiety in the family.
SA: So if in a DGH we have a baby who is floppy, we should call you as soon as we can?
MG: I would say it's important to do a clinical examination and try to find out whether there is coexisting weakness or not. Try to find out whether reflexes are present or not, investigate if you feel that there is a central involvement as well, or it mainly appears to be a a case of a peripheral hypotonia.
And there is a number of tests which can take place very easily, even in a DGH like CK, like thyroid tests or some baseline metabolic tests. And of course in parallel with investigation, we also start to address any problems that those babies have. For example if we have concerns about feeding and swallowing function, we need to put an nasogastric tube and ask assessment from speech and language therapy team.
And if we have concerns about the respiratory function, it's important to do a blood gas as soon as possible and escalate for further respiratory support if this is needed.
SA: I think that leads us really nicely onto your approach to treatment in these babies. Can you tell us a little bit about that?
MG: So, an important aspect of treatment is to make sure that those babies are safe. So, as I said before make sure that their respiratory function and feeding are quietly protected and safe. A baby with hypotonia can also be prone to infections. So this is something we need to have in our mind, even before we make the final diagnosis. We need to be vigilant and treat promptly when they appear any signs of respiratory infection. Those babies are also eligible, a number of them are eligible, for some special immunizations. Like babies with SMA who are on ventilatory support are eligible for RSV prophylaxis.
Sometimes this is quite rare, but it's important to highlight that babies and patients with some neuromuscular conditions may have a severe complication when taking general anaesthesia, which is called malignant hyperthermia. It is quite rare. And it appears in a very small number of patients with neuromuscular diseases. However, if we have to administer general anaesthesia in an infant before making a final diagnosis, it is important to discuss with the anaesthetics team about this possibility and discuss what option of aesthetic agents would be safer for those children.
And, of course, there is a number of cases of causes of hypotonia for which there is a definite cure, a definite treatment. As I said before, now we have available treatments for spinal muscular atrophy, gene therapies available, as well as treatment with antisense oligonucleotides. In the case of infantile botulism, as I said, we have the antitoxin, which we can administer and actually save the baby's life.
We have a number of metabolic disorders for which an enzyme replacement therapy is available, like in Pompe disease, for example. In the case of myasthenia gravis, congenital myasthenia or congenital myasthenic syndromes we have medications that we can administer like pyridostigmine and help with hypotonia, with floppiness.
And of course, there is also a number of other diseases like fatty acid oxidation storage disorders, where we can treat them with nutritional supplements like carnitine, for instance.
So, our treatment approach includes a combination of treatment of symptoms making sure the baby is safe. And also investigating if there is a definite cure for the underlying condition.
SA: We spoke a little bit about caveats earlier, but I was wondering if there were any other pitfalls that you wanted us to be aware of?
MG: We need to be aware that sometimes hypotonia may change from time to time. It might exhibit something like diurnal variation. It depends on the state of the baby. If the baby is distressed and irritable or if the baby is sleeping and is drowsy. So this can play a role. As well as there are some underlying conditions in which diurnal variation is a hallmark, for example in congenital myasthenia we will expect symptoms to get worse later in the day. So symptoms are better in the beginning of the day and get worse toward the evening. So this is something we can have in our mind when we assess a baby with strong suspicion of congenital myasthenia.
Another caveat is that although I said we have cases with central and peripheral involvement, we need to bear in our mind that we may have cases with a peripheral cause, but also associated involvement from the central nervous system. This can happen in a number of cases of congenital muscular dystrophy with the one quite severe condition called Dess Walker- Warburg syndrome where we can have prominent muscle weakness with high CK levels and also have very prominent findings from central nervous system like hydrocephalus, lisencephaly, and also problems from the eyes. So there is no black and white. We may have an overlap of manifestations in a number of cases.
SA: It sounds like quite a minefield, honestly, with a lot of overlap, but I think the approach you've given us is really kind of, I think the approach you've given us is really helpful and really precise and straightforward and definitely something that the general pediatrician can at least start to do before talking to you guys.
And thank you so much for laying it out in a way that makes it really clear and easy to follow.
I wanted to end, if it was okay, with some quick fire questions. So are there any classic exam questions that could pop up about the floppy baby?
MG: Yes. I would say that the very frequent question is to discuss about the causes of floppiness. It is important to be aware of central and peripheral causes, as we have already analysed. Another important question is about clues from medical history, which are important to guide our differential diagnosis.
SA: And do you have any useful resources that you would recommend?
MG: There are two useful webinars about the approach to floppy baby. One of them is available in the European Paediatric Neurology Society website. And the other one is available in the website of International Child Neurology Association for those who are members. And also the British Paediatric Neurology Association offers an interesting short course about approach to tone disorders in childhood.
SA: Amazing. I'll make sure all of those are linked in the description. And finally, what are your three takeaway learning points?
MG: The first one is always to examine the baby. If needed, come and examine the baby again and again. And don't forget to examine the parents of the baby as well. The second one is to focus first on what is urgent and what is treatable, for instance, it's important to make sure that we protect the respiratory function of a baby. And also it is important to diagnose first conditions for which there's available treatment, for example, in spinal muscular atrophy, in infantile botulism or in other cases of metabolic disorders. And the third one is be aware of the limitations about CK levels. So sometimes they may be affected by birth. So just have it in the background of your mind.
SA: Maria, thank you so very much.
MG: You're welcome. Thank you very much for the discussion.
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