Welcome to our presentation on Pediatric Hypertonia Management. My name is Katie Zurbach and I'm a Pediatric Rehabilitation Medicine Physician at Penn State Health Children's Hospital in Hershey, Pennsylvania. The second half of this presentation will be by Patricia Orm, a Pediatric Rehab Physician at the Children's Hospital of Philadelphia. Neither Dr. Orm nor myself have any financial disclosures. The learning objectives for today's presentation are to review oral antispasticity medications commonly used in pediatrics, as well as botulinum toxin dosing in pediatrics, and neurosurgical interventions for pediatric hypertonia. We will not be discussing orthopedic intervention for pediatric spasticity management. You may have noticed that we're utilizing the terminology pediatric hypertonia. This is common in pediatrics as it can be difficult to differentiate spasticity and dystonia, especially in our younger patients. Therefore, if it's unclear whether the movement pattern is spasticity or dystonia, many providers will utilize the general term hypertonia. If it's clear that the movement is spasticity or dystonia, that terminology will be used. The most common sources of pediatric hypertonia are cerebral palsy, acquired brain injury, followed by spinal cord injury, and genetic dystonia. As cerebral palsy is the most common disability of childhood, we will talk a little bit about our gross motor functional classification system in cerebral palsy. There are five levels of gross motor functional classification, or GMFCS, which we utilize to grade the level of function in cerebral palsy. They go from 1 to 5, with 1 being the least affected and 5 being the most affected. Children that are deemed level 1 can ambulate independently and traverse stairs without utilizing a railing. Children at a level 2 walk in most settings and are able to climb stairs independently, but utilize a railing. They may need some assistance for longer distances or a mobility device such as a walker or crutches, and they may use wheel mobility for longer distances, but they can ambulate in the community. GMFCS level 3, patients will use a handheld mobility device in indoor settings and often require a wheelchair for community settings. At GMFCS level 4, patients require physical assistance for mobility or are able to operate a power wheelchair without assistance. I like to think of these patients as patients that are able to walk for exercise, so may need a gait trainer or physical assistance for ambulation, and it may not be a functional means of mobility for them, but they do have some independent mobility. At GMFCS level 5, patients are transported in a manual wheelchair in all settings and have limited control of their head and neck and trunk, and are unable to transfer themselves at all independently. In pediatrics, we utilize many similar treatment modalities to adults, and the core of our treatment is often physical therapy, occupational therapy, bracing, and stretching. They're also very commonly orthopedic interventions, which will not be discussed today, and the oral medications, injections, and neurosurgical procedures, which we will be discussing today. Now I will review oral medications for spasticity and dystonia. There's a lot of overlap between medications used for spasticity and dystonia, both in pediatric and adult medicine. Our most commonly used medication for pediatric spasticity is Baclofen. This is FDA approved for children greater than 4 months of age, and is available as tablet, granules, as well as suspension. The suspension formulation of Baclofen is relatively new, and historically was not recommended to compound Baclofen due to concerns for uneven dosing. However, there are now three commercially available Baclofen suspensions, and I have not noticed significant issues with Baclofen dosing with these commercially available suspensions. The next most commonly utilized medication for spasticity and dystonia in pediatrics is Diazepam. As you can see, this is FDA approved for children over 30 days of age, and so we can use it in our younger patients, as well as our babies that are still in the NICU. This also comes in both tablet and suspension form, and we often utilize it for patients that are younger, or have other reasons to be on a benzodiazepine, such as our patients that are on seizure medications and need benzodiazepine bridge, or that have failed Baclofen treatment. Another medication commonly used for children, both with spasticity and dystonia, is Clonidine. Unfortunately, Clonidine does not come in a commercial suspension, and so it needs to be compounded if you need doses less than half a tablet, or 50 micrograms. It does also come in a patch, which is 0.1 milligrams for 24 hours, changed every five to seven days, as well as 0.2 milligram and 0.3 milligram patches. Half patches can be administered, but they have to be carefully counseled regarding how to administer a half a patch. Clonidine is approved for all ages, including preterm infants, and so is frequently used in pediatrics. Clonidine is also FDA approved for ADHD in pediatrics, and so can be utilized for our patients that have both attention issues and spasticity or dystonia, and so is very commonly utilized. It is also FDA approved for sleep onset in children with neurodevelopmental disabilities, and so is often used for that reason. For children with neurodevelopmental disabilities, the starting dose for sleep onset is usually 0.05 milligrams to 0.1 milligram nightly. And then getting to two more commonly adult medications utilized for spasticity, Dantroline and Tizanidine. Dantroline is only approved for children greater than five years of age, and like Clonidine, does not come in a suspension. And so for our smaller patients, requires compounding, and so it can be challenging to administer. Additionally, even though it's not thought to produce a lot of sedation, it can cause sedation in pediatrics, and so it doesn't have a significant benefit over baclofen for many of our patients. Again, it's also only FDA approved for children over five years of age, which limits its use in our children with cerebral palsy. Tizanidine is approved for children over two years of age, but is also not commercially available in a suspension form, and so dosing can be limited in our younger patients. It does have some standard dosing for our younger patients, two to 10 years old, with one milligram nightly, which would be a half of a tablet. So it can be utilized for that reason. Because Tizanidine and Clonidine have a very similar mechanism of action, we don't typically mix those two medications. So if a patient has other indications for Clonidine, such as sleep issues or attention issues, we may prefer to use Clonidine over Tizanidine. Now I'll move on to oral medications for dystonia and apoptosis, though we do use some of these medications as adjuncts for spasticity as well. Gabapentin is our most commonly used medication for dystonia as well as an adjunct for spasticity. Like Clonidine, it is FDA approved for all ages, and so is very useful in the pediatric population. It also comes in both tablet capsule form and a commercially available solution, which also makes it very useful for our younger patients. For Gabapentin, we typically start at five milligrams per kilogram per day, either as a single nightly dose or divided into three doses, similar to having either 100 milligrams three times a day or 300 milligrams nightly if you were starting the medication in an adult. You can increase as frequently as daily, and the usual effective dose is 8 to 35 milligrams per kilogram per day, for a max dose of 60 milligrams per kilogram per day or 3,600 milligrams per day, which is the max adult dose as well. I think Gabapentin can be a really useful adjunct for our patients that have mixed dystonian spasticity, as it can be unclear what the triggers are for some spasticity in our patients, and adding Gabapentin can sometimes minimize noxious stimulus when we're not really sure what's going on. Additionally, Clonidine and niazepam are really commonly used for dystonia in pediatrics, as again they are FDA approved for children that are very young and tend to have less side effects in pediatrics than they do in the adult population. The last three medications on this slide, of the three of them, only Trihexafenadil is FDA approved for pediatrics in the United States. Trihexafenadil is primarily used for dystonian athetosis and can be very effective for this, however, often dosing is limited by side effects. I find very commonly I see significant urinary retention with Trihexafenadil, and it can also worsen anxiety, which can be a struggle for our patients with dystonia, as often anxiety and dystonia are comorbid. Trihexafenadil also comes in an oral solution in addition to a tablet, which can be helpful for dosing. It's also the only FDA approved medication for dystonia and cerebral palsy. Carvodopa and tetrabenazine are not FDA approved for pediatrics in the United States. Carvodopa levodopa is most commonly used for dopa-responsive genetic dystonias, though it can be trialed for secondary dystonias related to cerebral palsy. It does come in both an OGT and an oral solution, which makes it slightly easier for titrating in pediatrics, though again, this would be an off-label use. I also tend to find that there are significant side effects in our pediatric patients for Carvodopa levodopa, especially GI side effects, and so this often limits utilization of this medication. Tetrabenazine is not approved for pediatrics in the United States, but it is approved in Canada, and so it was also utilized especially for dystonian apoptosis, more often apoptosis in my experience. This medication comes in a tablet form and does not come in a solution, however, the tablet does come in a relatively low dose and so can be utilized in our younger patients. Again, tetrabenazine can have significant side effects, including tardive dyskinesia, and so that can sometimes limit our utilization of this medication. Now we will talk about chemodenervation in the pediatric population. Onobotulinum toxin and abobotulinum toxin were the first two toxins approved for use in pediatrics, and are FDA approved for both upper and lower limb spasticity. Sometimes abobotulinum toxin is preferred in our pediatric population, as it has been shown to last up to six months, as opposed to a shorter duration of other toxins. In my personal experience, I have seen abobotulinum toxin last for over six months in some pediatric patients. This can be a great benefit to our pediatric patients, as some patients require anesthesia for injections, and there is some concern for ongoing damage to the muscle due to repeated injections. So the more we can limit injections in our pediatric patients, the more we prefer to do so. Incobotulinum toxin is also approved for the upper limb and salivary gland for children over the age of two, while rimobotulinum toxin is not approved in pediatrics, though it is often used in patients with concern for antibody formation, or with decreased response to type A toxins. All the toxins are typically dosed in units per kilogram, with the total max dosing lower than the total max adult dosing. However, adult dosing can be used for patients that are over 60 kilograms, and therefore considered to be adult size. As you can see, none of the toxins are approved for children under the age of two, however, toxins are also used for children under the age of the two off-label, especially for children with birth brachial plexus palsy and torticollis. Torticollis is usually treated with one to two rounds of injections, and then referred for surgical intervention, and birth brachial plexus palsy is typically to work on co-contraction, so to help patients separate the control of co-contracting muscles, or to try to avoid development of glenohumeral stability by injection of the shoulder muscles. Similar to adults, guidance is typically used in pediatric chemo-denervation, however, given the smaller muscle volume in our pediatric patients, there is more tendency for toxin spread, and so if injections are not being performed under sedation, sometimes only anatomic guidance is used to shorten the duration of time the needle is in the muscle, so by reducing pain. This is typically used in large muscles that are easy to identify anatomically, such as the gastrocs, or adductors, as well as in areas where the muscles have similar functions, such as the flexor compartment. Additionally, often in our unsedated patients, EMG guidance is preferred to e-stim, as e-stim can be painful and difficult to explain to our younger patients. If injections are being performed under anesthesia, however, often e-stim is preferred as EMG signal can be blunted under anesthesia. There is emerging use of ultrasound guidance in pediatric chemodenervation, however, it is still not the primary form of guidance utilized. Here you will see some recommended dosing for botulinum toxin in the lower limb. I also want to mention that there is evidence that botulinum toxin injection in pediatric patients with cerebral palsy can cause long-term alterations to the muscle structure, including atrophy and infiltration of fat into the muscle. And so we try to be as conservative as possible in our pediatric patients, repeating injections only as needed as opposed to on a schedule of every three months, as you may see in the adult population. You can see that for onobotulinum toxin and abobotulinum toxin, the dosing is slightly different, often with higher number of units per kilogram for abobotulinum toxin. Again, there's not a direct conversion between different toxins, and so I typically rely on the manufacturer recommendations and this article by Satila in order to design my botulinum toxin plan, depending on which toxin I am using. And here you will see recommendations for upper limb dosing. And here you will see recommendations for upper limb dosing. Again, you'll see that it is somewhat related to the volume of the muscle, though for abobotulinum toxin, it's pretty similar for all muscles in the upper limb, whereas with onobotulinum toxin, there's a little bit more variability. You will see that in the total dose per session for combined upper and lower limb, for onobotulinum toxin is 10 units per kilogram or 340 units, which is lower than the 400 units for an adult patient. However, you can use the adult dosing for children over 60 kilograms. For children that you're utilizing abobotulinum toxin, the max total dose per session upper limb and lower limb combined is 30 units per kilogram or 1,000 units. Again, for both onobotulinum toxin and abobotulinum toxin, adult dosing can be used for patients over 60 kilograms. Both phenol and ethanol neuralysis are also utilized in pediatrics. Phenol neuralysis has pretty good literature to support improved spasticity and gait in children with cerebral palsy. And most commonly, the obturator nerve and the medial hamstring branch of the sciatic nerve are addressed with phenol neuralysis. There has also been some report of utilizing phenol for the musculocutaneous nerve, but this is less common. Because of the need for electrical stimulation to accurately target the phenol, children often tolerate these injections poorly and they are often done under anesthesia. The dosing recommendations are not well studied. However, the recommended dose is less than 30 milligrams per kilogram or 0.5 mLs per kilogram. It has been shown that less than 5% of children who receive phenol injections report dysesthesia. We have seen that use of electrical stimulation and ultrasound can minimize the amount of neurolytic used. And when you're using electrical stimulation, you want to see response at a very low electrical stimulation, typically at 0.2 to 0.5 milliamps, as opposed to when using electrical stimulation for botulinum toxin, where you might simulate in the range of 5 to 10 milliamps. And then you would continue injecting the phenol until you see extinguishing of the electrical stimulation. This is usually around 0.5 to 1 mL of phenol. The other concern for doing phenol and ethanol neuralysis is that eye protection by everyone in the room must be used to the risk of blindness if you were to get phenol in your eye. There are reports of ethanol neuralysis as well, but phenol neuralysis is more common in pediatrics. And for ethanol neuralysis, it's reported to use 5 to 10 mLs of 5,200% ethanol into each muscle treated. You can see our equipment utilized for phenol neuralysis, including electrical stimulation, our stimulating needle, our phenol, and then also additional botulinum toxin. Often, since we are putting children under anesthesia for the neuralysis, we will do combined phenol and botulinum toxin, as you might do in an adult patient. Now we will transition to discussing a few of the most commonly used surgical management options for treating spasticity and dystonia in the pediatric population. This will include a review of intrathecal baclofen, selective dorsal rhizotomy, combined ventral dorsal rhizotomy and deep brain stimulation. Of note, there are also orthopedic surgeries that address musculoskeletal deformities often associated with hypertonia, such as surgeries treating contractures or hip dysplasia. However, these will not be further discussed in this lecture. So first, we will begin with discussing intrathecal baclofen. Baclofen works by causing inhibition of the monosynaptic reflex arc at the spinal cord level. As in the adult population, a subcutaneous baclofen pump is typically placed in the abdomen with a catheter that then runs from the pump to the intrathecal space, typically between the lower thoracic and upper cervical levels. However, in the pediatric population, catheters tend to be placed at the higher spinal levels and even in the ventricles at some institutions. Again, as in the adult use of intrathecal baclofen, the pump can be programmed for simple continuous constant dosing or variable flux intermittent dosing. The total daily dose typically varies between 50 and 1,500 micrograms per day, depending on the patient's response. Now, prior to implantation of the device, depending on the surgeon, medical facility, and family preference, a test dose of 50 to 100 micrograms of intrathecal baclofen may be given via lumbar puncture to assess the patient's response to intrathecal baclofen and help decide on whether or not to proceed with pump implantation. However, because there tends to be high rates of positive responses to test doses, as well as poor predictability of the test dose response when compared to response with intrathecal baclofen pump, some providers may only perform a test dose if the family or patient requests, or if the patient has an atypical diagnosis. Risk to placing an intrathecal baclofen pump include infections, catheter dysfunction or migration, and CSF leaks. Now, when thinking about what patients might be good candidates for intrathecal baclofen, in the pediatric population, a major consideration is whether or not the child's size can actually accommodate the intrathecal baclofen pump, which is about 3.4 inches in diameter and 0.75 inches in depth. So because of this, typically a child must weigh 15 kilograms or more. But even with this weight recommendation, the child may have anatomic reasons, such as severe scoliosis, limiting pump placement. Additionally, if a child has insufficient subcutaneous tissue, the pump is at risk for causing skin erosion. Intrathecal baclofen pumps can treat either spasticity or dystonia. However, intrathecal baclofen is typically thought to be more effective at treating spasticity rather than dystonia. And from a functional viewpoint, the patient may be ambulatory or non-ambulatory. As with use in adults, those receiving intrathecal baclofen will also need to feasibly be able to return to the medical facility for regular follow-up. This will include baclofen refills at a minimum of every six months and eventual pump exchange towards the end of the pump's battery life, which is typically about every five to eight years. Now we'll talk about selective dorsal rhizotomy, or SDR. The idea here is a portion of the sensory fibers, which are contained within the dorsal roots, are transected or cut. By doing this, the monosynaptic reflex arc at the spinal cord level is decreased, which results in a decrease in spasticity. Because in the surgery, only the dorsal or sensory fibers are affected, the long-term outcomes for patient's motor function is theoretically preserved. And by severing only a select amount of sensory fibers, sensation is also largely preserved. So how is this actually performed? The surgeon completes a one to two level laminectomy at the level of the conus medularis, and then is able to access the dorsal roots at the L1 to S1 or S2 level, making sure not to dissect lower in order to avoid causing bowel or bladder dysfunction. Then, by using intraoperative EMG, rootlets with the most abnormal responses to the electrical stimulation are identified and transected. Typically during this procedure, 25 to 60% of the dorsal rootlets are transected. Interestingly, the specific level of roots dissected, the percentage of rootlets severed, and the utility of monitoring with intraoperative EMG are debated and vary across different sites. Risks associated with this procedure include transient weakness, sensation changes, as well as transient urinary retention, and more rarely CSF leaks and wound infections. When thinking about the right patient selection for this procedure, SDR has been shown to only help improve spasticity, not dystonia. Specifically, a patient with spasticity secondary to cerebral etiology rather than spinal cord etiology. Classically, a patient with spastic diplegic cerebral palsy is an ideal candidate because SDR specifically addresses hypertonia in the lower extremity. Although interestingly, we have seen that patients with both upper and lower extremity spasticity have been shown to have improvement in their upper extremity spasticity as well, following SDR. Now, the reason SDR is avoided in patients with dystonia is because SDR may further unmask the underlying dystonia and can actually cause worsening or exacerbation of dystonia. Also, this procedure has been found to be most helpful for those who are at baseline ambulatory, either independently or with assistive devices. So typically talking about children who are at the GMFCS level of one, two, or three, with a main goal to improve their gross motor function, which includes not just walking, but also sitting and standing. Although the surgery can also certainly help with decreasing pain and the development of contractures or hip dislocation due to decreased hypertonia. The target age for this procedure to be performed is between four to 10 years old. And the theory here is that at a younger age, the child's brain has more plasticity and improved chances of being able to change motor patterns following the procedure. Now, in order to significantly change motor patterns following the procedure, again, with a goal to improve motor function, an important component of post-surgical recovery will need to include intensive therapies with physical therapy and occupational therapy. And as such, it is important to consider the feasibility for the patient to access these services, as well as considering the cognitive ability of the patient to engage in this level of therapy. Now let's talk about the ventral dorsal rhizotomy, also referred to as a combined rhizotomy. A ventral dorsal rhizotomy is performed very similarly to the SDR. However, this time the surgeon severs both the sensory and motor rootlets, again, from the level of about L1 to S2. But the surgeon will typically transect a higher percentage of rootlets as compared to SDR, around the order of 50 to 80% in a non-selective manner. So as you might imagine, this procedure will have a more profound impact on tone than SDR alone. Because both the ventral and dorsal rootlets are severed, the combined rhizotomy has been found to be effective for treating both dystonia as well as spasticity. So remembering here that the SDR is used only for tone related to spasticity, whereas the combined rhizotomy can be used to treat those with mixed spasticity and dystonia. Of note, similarly as in SDR, we have also seen improvements in the upper extremity tone following the combined rhizotomy. Typically, the ventral dorsal rhizotomy is performed in a child over the age of four, who at baseline is typically non-ambulatory, such as a patient who is at a GMFCS level of four or five. The primary goal of the combined rhizotomy is to treat tone that is significantly impacting the patient's and caregiver's quality of life. In this way, we can think of a combined rhizotomy as more palliative in nature, rather than used to improve baseline motor function, as is the case with the SDR procedure. So we can think about a combined rhizotomy for patients who might be too young or underweight for an intrathecal baclofen pump, or a patient who may not feasibly be able to return regularly to a medical facility for ongoing pump management. And finally, we wanted to touch briefly on deep brain stimulation. Deep brain stimulation theoretically works by stimulating the inhibitory pathways found in the basal ganglia via electrode placement so that the overactive neuronal patterns are decreased. The patient should be seven years of age or older and may be ambulatory or non-ambulatory. When using deep brain stimulation to treat hypertonia, it is only used for tone related to dystonia, not spasticity. Notably, deep brain stimulation has been found to be much more effective at treating primary forms of dystonia rather than secondary, such as dystonia due to cerebral palsy. Now we will end with a review question. A six-year-old boy with spastic diplegic cerebral palsy who ambulates with a posterior walker presents to clinic for ongoing tone management. He has had some beneficial response to oral baclofen, however, dosing has been limited by side effects. He and his family live in a rural area and they share with you that it is difficult to regularly come to the medical facility for appointments. What is the next most appropriate intervention for his tone management? A, intrathecal baclofen, B, chemo-de-innervation, C, selective dorsal rhizotomy, or D, ventral dorsal rhizotomy. The answer is C, selective dorsal rhizotomy. The patient is considered an appropriate candidate for SDR given his age and functional status, meaning he's ambulating with assistance. Because there is no evidence for dystonia, and again, because he is ambulatory, a ventral dorsal rhizotomy would not be indicated. Importantly, because the patient lives in a rural area and is unable to return for regular follow-ups, intrathecal baclofen and chemo-de-innervation are not ideal long-term options for his care. Thank you for spending some time with us today to review pediatric hypertonia management.

pediatric hypertonia

antispasticity medications

botulinum toxin

neurosurgical interventions

Baclofen pumps

selective dorsal rhizotomy

dystonia management