So welcome everyone. This is our monthly lecture series. So we do this on the second Tuesday of the month at noon central time. So we just try to keep it somewhat regular for the trainees so that they can have time blocked for this. But these lectures are available on the AAPM and our online learning portal, usually a couple of days to weeks after we complete this lecture. And then that is also how you will get your CME credit. So you have to go on and complete the survey there. So my name is Emily Kivlingan. I'm the education vice chair of the AAPM and our Peds Rehab community. Our next lecture will be spinal muscular atrophy next month with Dr. Mary Lynch. And then June 11th, we actually have an open slot. So if anybody has interest in giving a lecture, feel free to shoot me an email. But today I'm very excited for our lecture. So today we're talking about perks as well as sympathetic hyperactivity after pediatric brain injury. I feel like we all maybe do this a little bit differently. So I think this is a great topic to talk about on the national level. So I'm really excited to hear how you guys manage it down in Texas. So today talking will be Dr. Simraj Abed. She is currently in attending in Pediatric Rehabilitation Medicine at UT Health. She completed medical school at the Toro University of Nevada and completed her physical medicine and rehab residency at Wayne State University School of Medicine and then did her Pediatric Rehabilitation Medicine Fellowship at UT Southwestern and has now stayed in Texas. So I will hand it over to you. Thank you so much. Yes, kind of all over, but back in Texas. So as Emily mentioned, we're gonna be talking about perks as most sympathetic hyperactivity after a pediatric brain injury. And as she alluded to, we all do it differently. I think it depends based on your training and what you're more comfortable with. So I definitely wanna start this lecture off with some poll questions and bear with me because we are definitely gonna try to see if it will launch. So our first poll question, it's what's typically used as first line for paroxysmal sympathetic hyperactivity at your institution. Well, I should actually go back there. Let's see. Can you guys see the poll? Okay, good. I see some answers coming through. We'll give it another couple of seconds. Can you guys see the results or no? We cannot see the results. Okay. So it looks like 50-50. So I'm getting about 10 responses for clonidine and 11 for propanolol. So propanolol edged just a little bit ahead of that. All right, I guess I can share results. Can you guys see that now or no? Yes, I can see it now. Okay. So that's the first one. Okay, awesome. The second poll question is how often are you being consulted for storming at your institution? So storming or PSH, including acute care. Let me launch the poll one more time. So daily, a few times a week, so daily, a few times a week, a few times a month, less than 10 times a year. Okay, it looks like a lot of a few times a week. So this is definitely the audience for this chat. Let's share the results. So a few times a week is the overall winner here. And then we'll go to the next poll question. Let's see. Okay, so where are you treating PSH or storming most often? So ICU or the PICU, general pediatric inpatient floor, IPR, or outpatient. So it looks like the majority are saying ICU, PICU, which again, that's been my experience as well. Great, glad we got a little bit of an under, kind of understanding of who all is in the audience. So definitely proxismal storming, proxismal sympathetic hyperactivity or storming is institution specific. Some of the objectives for today's talk is we're gonna go a little into the definition of PSH, the possible pathophysiology of storming that has been put forth in literature. Then we will review the clinical manifestation of PSH and diagnostic tools that can be utilized to identify PSH. And we will translate knowledge gained about the diagnosis into management of pediatric patients with PSH. Lastly, we'll discuss ways to distinguish PSH from other diagnoses. So there is a paucity of literature on PSH in pediatrics. This can be due to multiple factors, such as under diagnosis, under recognition, inconsistent terminology, and underutilized diagnostic criteria. This is a brief overview of what will be discussed today and hopefully exploring some of the key pieces of PSH will help providers, meaning you guys, in applying the knowledge to management of PSH after acquired brain injury. I will likely interchange PSH with dysautonomia and or storming throughout the lecture just for brevity. So they are all one in the same when I'm interchanging them. I wanted to start off the presentation with a brief, interesting consult we had in acute care during fellowship in which peds rehab played a integral role in the management of not only the patient's tone in DOC treatment, but management in her intractable storming. I'm not gonna go into her entire course because it was pretty complicated with numerous specialists, but we'll focus a little bit more on the management of PSH. So we had a 17-year-old female, past medical history of UC, recent diagnosis of EBV, admitted to acute care with 35-pound weight loss, altered mental status, and imaging concerning for ADEM. Initial improvement with steroids and PLEX, but declined a week later with worsening on imaging. And she fell into a coma and then was more in a mentally conscious state. She was diagnosed with EBV-positive granulomatosis, and she had a very complicated prolonged acute care course. PMNR was brought in around day 10 of admission for actually tone management initially. It wasn't for storming concerns. Around week five of admission, we did notice that she had clusters of intermittent fever, tachycardia, hypertension, dystonia, and they also didn't update an MRI at five weeks post-admission, and she had new lesions. So the initial spasticity management we started was with Baclofen, we increased that. She also has some dystonia for which we added some bromocryptine as well to help her with the arousal. After we noticed the storming, we went ahead and titrated up on the Baclofen. Her episodes actually continued to worsen no matter what we tried. We added in Neurontin, Valium was scheduled. We upped the bromocryptine. Propanolol actually seemed to be the most helpful with the fevers, but we were dose-limited by the effect on her heart rate. So she was very bradycardic, and I believe she had some lesions in her brainstem which contributed to that. Her final regimen was pretty high for some of our storming kiddos. So she was on schedule Neurontin, Baclofen, Bromo, Valium, as well as PRN-Valium and Propanolol. This was a case in which I feel like we were seeing her almost every other day, if not every day, just to adjust her medications and see what she was responding to. This final regimen did help her overall storming episodes, but unfortunately she did pass away just due to the extent of her disease. And this is, you can see her, one of her last MRIs. So you can see the disease burden, and we postulated that the widespread evolving injury was what made it difficult to manage her storming. She just kept having new lesions with each subsequent imaging. So when we talk about PSH, there's a lot of literature out there, but there's not as much concrete evidence. The first published case of PSH was most commonly attributed to Wilder Penfield in 1929. Though his case was a mix of sympathetic and parasympathetic features, the actual earliest and clearest report with the features of the revised definition was 25 years later. There have been calls for consistent nomenclature for more than 30 years, and frequently it's still referred to as dysautonomia storming, as I mentioned earlier, especially in discussions among providers for shorthand. And up until 2010, dysautonomia was the dominant term in published literature. PSH was first introduced by Rabenstein in 2007, and in 2014, Bagley et al put forth a consensus position which broadly defined PSH as a simultaneous proxismal transient increase in sympathetic and motor activity. PSH can occur from any focal or diffuse severe brain lesion. So it could be trauma, infection, encephalitis, anoxia, hydrocephalus, pretty much any injury to the brain. The clinical presentation does not actually appear to differ depending on the underlying etiology. However, there have been frequently belief, there have been frequent reports that PSH occurs more after traumatic brain injury, but then there are other studies indicating that anoxic brain injury tends to have a higher prevalence of PSH. But as TBI is more overall prevalent cause of brain injury, there's probably a higher incidence of PSH after TBI. No one true lesion has been pinpointed to be the most common cause, but PSH is most often associated with overall burden. And of course, it's widely held that PSH is a diagnosis of exclusion and that early recognition and treatment of dysautonomia can prevent secondary injury. And then we definitely want to note that it is different than AD and SCI patients, though it has some analogous features. So there have been over 30 different names in the literature for PSH. However, in 2010, they did settle on proxismal sympathetic hyperactivity. In 2014, the Bagliatelle Consensus Review supported the use of PSH as having three advantages. Firstly, it was more specific in contrast to other terms like dysautonomia or sympathetic storm. Second, it was not preempting an underlying pathophysiology. So for example, autonomic diencephalic epilepsy or hypothalamic midbrain dysregulation syndrome. And then third, it accurately portrayed the conceptual definition of what was happening in contrast to other phrases such as proxismal sympathetic instability with dysautonomia. So the pathophysiology of dysregulation of the autonomic nervous system is not completely understood. And there are suggested mechanisms behind PSH, but they are not conclusive and they are still being studied. What we do know is that elevated catecholamine levels have been documented in PSH. There is an excessive activation of the sympathetic system which leads to end organ activation, including adrenal glands, which in turn release those catecholamines. The central and peripheral release of the catecholamines leads to clinical manifestations that we are used to seeing, including hyperthermia, hypertension, tachypnea, diaphoresis, and the hypertonic conditions like spasticity and dystonia. Dysautonomia is often triggered by a noxious stimuli, but there are numerous possible triggers. And some of the most common ones that we think about or we want to keep in the back of our mind when we're assessing patients is pain, bowel, bladder, wounds, respiratory secretions. So the pathophysiology, again, of PSH is suggested. It's not conclusive. Most of the popular theories are some version of the disconnection theory. The theories tend to center around the diencephalon, so the thalamus and the hypothalamus, which are thought to be central excitatory foci during proxismal episodes. And then of note, the diencephalon is involved in temperature regulation. In the disconnection theory itself, it's thought that the disruption of pathways between the cortex and the hypothalamus actually start the cascade. It's assumed that brainstem excitatory centers are released from the higher control, and then there is a resultant hypersympathetic state. In the excitatory-inhibitory theory or model, it's also an example of a disconnection theory model. There is thought to be excessive excitatory output due to damage to the central inhibitory structure. So the lesion in the inhibitory centers in the brainstem and diencephalon reduces the descending inhibition to the afferent sensory information from spinal cord circuits. This will result in amplification of the normally non-susceptive afferent sensory information from the periphery and leads to the overexcitation of the sympathetic nervous system's response and causes. So essentially, the excitatory-inhibitory theory is saying that hyperactivity originates at the spinal cord level in a process analogous to AD. And this theory does explain the pathologically increased and extended allodentic responses to stimuli, both non-nociceptive and nociceptive. And there has been evidence that the catecholamine level can rise 200 to 300% above normal during these episodes. So that supports the overactivation of sympathetic nerves, though again, the mechanism of the actual activation is unclear. So epidemiology, a lot of the literature when I was updating this lecture was definitely based on adults. Before a consensus definition was reached, PSH was described from anywhere to eight to 33% of adults after their sedation had been weaned. It has been described in about 13 to 14% of children, though the new consensus definition has not been widely used for pediatric patients with severe TBI. There were some studies that I wanted to point out. In 2018, the Alofessin et al. study showed the likelihood of PSH was more prevalent in severe TBI PD patients than previously reported, and they found it prevalent in up to 20%. 2015 Pasi et al. retrospective cohort study on PD rehab patients specifically found anoxic brain injury etiology more frequent in patients with PSH. But then there was a 2012 pediatric large case series with Kirk et al. and they found that storming after TBI was around 10%, but after cardiac arrest was 31%. So all that to say the true incidence and prevalence is not known, and it's likely due to confounding symptoms of other acute processes such as sepsis, but also differences in study design methods and patient population among other factors. In adults, we see PSH more common in males and younger patients. It's also associated with lower GCS values as well as longer hospital stays, longer ICU stays, and higher infection risks. In children, especially in rehab, PSH is associated with prolonged rehab, longer duration of coma, and greater frequency of late death. Higher late mortality is likely secondary just to the higher rate of comorbidities. So some of the characteristics that are definitely important to note for PSH, it usually develops in the acute phase following brain injury as early as the first week after ABI. In recent prospective cohort studies, they found storming to be occurring on average about six days post-injury, and typically in the ICU when they're starting to wean sedation. Individual episodes of PSH Individual episodes can vary in intensity and duration, but rarely do they persist for more than several hours per episode. Episodes can last anywhere from seconds to minutes to hours. Some studies have found ranges from three minutes to two hours, and averaging 30 minutes, and an average of five times per day. The duration of PSH overall is variable, though majority have a reduction of storming within the first few weeks, but there have been some reports of PSH lasting from less than two weeks to about six months, and some rare reports of it lasting into years. The occurrence will diminish over time. However, spasticity and dystonia can often persist after resolution of PSH. And as I talked about, there's overall differing opinions on whether it's more prevalent in patients with hypoxic and anoxic brain injuries versus traumatic brain injuries. It's really just dependent on which piece of the literature you're reading. So this conglomerate of symptoms is reported in about 10 to 30% of brain injuries during the acute phase. It's commonly seen after severe brain injury, so we think low GCS, anywhere from three to eight. Ranchal levels of less than or equal to four or longer coma durations. Also brainstem injuries or diffuse axonal injuries. And so this is what we would typically see in an episode of PSH. These are some additional features that may be seen. It could be things such as arrhythmias on EKGs, elevated white count without infection, elevated catecholamine levels, neurogenic lung disease, excessive salivation, even crying and hiccups, yawning and sighing have been seen during these episodes. The symptoms can be alarming because they can mimic things such as sepsis, impending herniation and or epileptic seizures. And we also want to make sure we're managing symptoms such as the arrhythmias or tachypnea and hyperglycemia because they can actually increase risk of impaired cerebral tissue oxygenation and that can lead to secondary brain injury. Persistent hypertension also increases the risk of secondary brain injury through cerebral edema, expansion of hemorrhage or anoxic injury from cardiac dysfunction. So it's important to recognize these symptoms early and manage them as best as possible. As we talked about, storming is a diagnosis of exclusion. There are no labs or tests that will confirm the diagnosis. However, there have been multiple sets of diagnostic criteria proposed, though there isn't one set that is widely accepted for practice. This diagnostic criteria was initially proposed in adults. And overall, the fundamental diagnostic criteria of PSH are characterized by storms of diaphoresis, hyperthermia, hypertension, tachycardia, tachypnea and marked agitation accompanied by hypertonia or extensor posturing. So symptoms we just discussed are typically part of the diagnostic criteria. They may just vary a little as far as which ones are included, depending on what, again, what literature you're reading. Additional aspects of diagnostic criteria included in most versions are that there is at least one cycle per day for at least three days and that we should be ruling out other conditions as they can mimic other diagnoses. And so just to see if everyone was paying attention, we have a question. So common clinical features of PSH include all of these except, let's see if I can launch that, if you guys can see that. Awesome. Let me end that really quick. So yes, bradycardia. Okay. All right. We have a few more of these. So just to see. So as mentioned, currently there isn't one set of diagnostic criteria that's widely accepted for clinical practice. However, in 2014, Baglia et al created the PSH assessment measure, which includes two components. So you have the diagnosis likelihood tool, or DLT, to address the probability of diagnosis and you have the clinical feature scale to assess the severity of clinical features. The CSF will measure heart rate, respiratory rate, blood pressure, temperature, sweating, and tone. Greater than 13 is categorized as severe. The DLT has 11 diagnostic items as listed and each being one point. The numerical output of these two components added together will help estimate the diagnostic likelihood of PSH at that point in time. This tool was designed to be able to assess patients continuously. So from ICU into rehab for serial use, which can help evaluate treatment efficacy. And ideally, this should be used daily at a standardized time. For the PSH AM score, greater than 17 means PSH is probable. Eight to 16 is possible, and then less than eight, it's unlikely. And then this slide has an example of just how to add it together. And for this patient, they did get 22 as a combined total, so PSH probable. There we go. So of course, we want to know what our pediatric patients, or what we should use for pediatric patients. In the same group proposed the clinical feature scale for pediatrics, given that the normal range for vital signs differs based on age. And this one is typically used for PD patients up to the age of 15 years old. So in place of the other CFS, you would use this. And for 16 and up, you could use the adult version. So some of the syndrome characteristics that I feel are important for providers to be aware of, not only just for the pediatric rehab providers, but also our colleagues in acute care, is that these proxismal episodes may be provoked or there could be some external trigger. 72 percent of PSH episodes have been associated with a trigger event in certain cases. These episodes can vary in intensity. They can persist for weeks, persist for months at a time. So they're not all in the same, all the episodes won't be the exact same. The onset of course varies, but it's on average about six days post injury. And it's more frequent in younger patients. And they typically have normal resting vital signs between episodes. Another thing to note is that resting energy expenditures can be up to three times the normal. So nutritional optimization is something that definitely needs to be looked at. Over time, episodes will become less frequent, but they may last longer. You definitely want to rule out any possible life-threatening illnesses that may appear similar in nature to PSH. And then if your symptoms are persistent without these paroxysmal episodes, then dysautonomia is actually unlikely. So management, that's what we really care about. Management centers around ultimately decreasing the sympathetic outflow. The most important step will always be to determine clinical urgency in which symptoms need to be treated. So if they're having airway, breathing, or circulation concerns, they likely need emergent or immediate attention. And hopefully in this case, they'll be in the ICU with close monitoring. The pediatric early warning score can help identify urgent cases. But it's usually institution-specific and it's not typically validated. Overall, urgent cases require IV benzodiazepines such as diazepam. But there are other medications that we'll use in non-urgent cases. For cases that can wait 20-30 minutes, we can use as needed propanol or clonidine. Included for reference on this slide, I really like this graphic. It is the clinical algorithm for dysautonomia. It's from the papers by Drs. Burton and Morozova. It's a really great read for even community pediatricians. It goes more into kind of how to manage storming. After addressing the urgent and emergent issues, the next step is to identify and treat any precipitating conditions or noxious stimuli. So do they need cathing? Do they need an enema, pain medication, and so on and so forth? Then you want to focus on ongoing management and maintenance. So you want to look at environmental modifications. Does the room temperature need to be adjusted? Do they need some blanket removals? Does it need to be a more low-stim environment? You want to work on regulating sleep-wake cycle. So lights on, shades open during the day, reverse at night, trying to group cares, other non-pharmacological interventions like passive range of motion with therapies, massage, positioning, splints. Then you finally want to address medications, which we'll go more into in just a bit. Throughout this algorithm, you should be reassessing the patient, and ultimately you want to mitigate any future PSH episodes if possible. This is another great example of a clinical algorithm for suspected PSH. This one is from U of Wisconsin. I don't know if there's anybody here from Wisconsin, but I definitely really like this algorithm as well because it's very easy to follow. And they also have a PSH event management algorithm that, again, is very easy to follow for whether you're in the ICU or the inpatient general PD floor or even in rehab. So management of PSH in children especially is empirical or anecdotal. It's poorly understood. No drug is universally or even predictably the most effective. Treatments with consistent, qualitative, efficacious, or reproducible results have not been developed, unfortunately. Most patients require multiple drugs with potentially complementary roles. For example, in the pediatric rehab setting, some studies have found that clonazepam, hydroxazine, you know, are the best drugs to suppress PSH. There's other evidence out there that supports the use of beta blockers, clonidine, and gabapentin. Typical approach definitely varies by training institution. That's why I wanted to start off with those poll questions and see what people are more apt to using or more comfortable using. Maintenance first-line agents are typically propranolol and clonidine. Propranolol is lipophilic. It has been independently associated with lower mortality than other beta blockers. It's also been shown to reduce the frequency and severity of storming episodes. Propranolol will decrease catecholamine levels, so decrease heart rate, blood pressure, respiratory rate, temperature, as well as the cardiac workload and metabolic rate. Propranolol has been associated with improvement in GCS scores, diaphoresis, and posturing. One thing to note, you do want to watch out for possible bronchospasm in patients with asthma. They have found that selective antagonists like metocolol are not as effective in mitigating this autonomic dysregulation. For clonidine, we know it's an alpha-adrenergic agonist. It acts both centrally and peripherally, so it will decrease blood pressure and heart rate, as well as circulating catecholamines. It does not have much effect on temperature, and there have been challenges with hypotension and bradycardia between paroxysms, making clonidine use and titration a bit of a challenge. Personally, I don't know what other people's experience is, but for clonidine, I've found a lot of benefit in refractory tachycardia and hypertension when it's being weaned, as well as some difficulty with prolonged weaning schedules in some of our severe brain injury patients. So I'm more apt to use propranolol over clonidine, but there are times where a patient comes from the ICU already on schedule clonidine or clonidine patch, so it's something just to make note of. There was a study called DASH after TBI. I believe it was out of Vanderbilt. They looked at a combination of propranolol and clonidine compared to placebo, but when I read the results, there were actually no significant differences in the outcomes, which was ventilator-free days versus placebo group, but it would have been a great study to, you know, if there was some difference just to help put a little bit more evidence-based medicine out there for management of storming. Romocriptine is often used after propranolol or clonidine, so it is a dopamine agonist. It can definitely help lower blood pressure. It also can help with some alertness in patients who are in the disorders of consciousness. There is a reported side effect of diarrhea, and dosing is very variable. Beyond the first three we mentioned, tone medications certainly have an important role. Overall, we try to avoid scheduled or around-the-clock benzodiazepines, even though it is often a go-to in the ICU, as they can impact cognition negatively. Opiates tend to also be a last resort due to their potential to impact cognition, but there have actually been some studies that have shown the majority of proxisms in patients with PSH are allodenic responses to external stimuli, so pain with movement or pain just from tone. And morphine has been frequently used as a first-line treatment to suppress the allodenic responses, as it is the most efficacious in this class. And there are times when patients are dose-limited by propranolol or clonidine, where we optimize tone medications, and I've had them use morphine PRN for episodes lasting longer than 15 to 20 minutes. Baclofen, we know, is active at the inhibitory interneurons in the spinal cord. It's often used in patients with refractory PSH or concurrent tone. There are, I think, three small prospective observational trials in one case series on ITB itself. There has been some strong evidence for the use of intrathecal baclofen, but because of the intervention being invasive, costly, and not always available, as well as reported complication rates from anywhere to 20 to 50%, oral medication trials are typically recommended as first-line. This isn't a poll question, but I'm also curious as to whether anyone here, institution-wise, has used ITB to manage PSH episodes. You can certainly type it in in the chat, and we can discuss that towards the end. Tone can be a symptom, but also a trigger, so we often time tone management meds and schedule them as importance maintenance tool. Dantrolene has been shown to be useful, particularly for posturing by reducing intracellular calcium concentrations. I've also seen hydroxazine used, but that's more typical when there is a concurrent psychomotor agitation. Our very, you know, our families often do their own research, and I think one out of three families with patients with brain injury will ask about hyperbaric. Unfortunately, there's very limited data. When I was doing some research, I only found a small case series in China that looked at hyperbaric oxygen for paroxysms and posturing, but they had unequivocal results, and I didn't find any other evidence out there regarding hyperbaric oxygen's role in PSH. This table I really like because it shows not only commonly used medications and their mechanisms, as well as what symptoms they treat and side effects, but it does break down dosing in children and adults. I know many of us take care of teenagers that are essentially adult size, so it's nice to have this reference, especially when it comes to dosing. And this was also from Dr. Burton and Dr. Morozova's article. Okay, the next question. Let me pull up the poll. So which of these statements is true of the commonly used medication propranolol? Oh, it won't let me launch it. Oh, I guess you guys can just shout it out because it won't let me launch. Let me try to, wait, oh, there it goes. There it goes. Sorry about the technical difficulties. Okay, let's give it a few seconds. So yes, it reduces heart rate and blood pressure. Remember, it's not a selective beta-1 adrenergic receptor, metoprolol is. That's why it works so well, is it's not a selective beta blocker. And then, okay. Which of these medications is a good choice for abortive treatment of paroxysmal episodes? That's long. Let me launch. Ooh, someone did haloperidol. Okay and that so yes morphine is probably the best choice right now out of this group as far as abortive choices. Someone did do haloperidol I don't know who it was but haloperidol has been has fallen out of favor I think even when I was in residency it has shown to have negative impact in brain injury recovery so we definitely try to avoid haloperidol or haldol use and then launch the next one oh sorry which of these medications is good for abortive no I just did that one I thought there was another one okay just kidding uh okay so the three main goals when it comes to treating patients with PSH is to one avoid triggers that provoke the proxisms as best as possible mitigate the excessive sympathetic outflow and to address the effects of PSH on other organ systems through supportive therapy so supportive therapy is definitely important to address longer term consequences this can include therapies positioning ranging to prevent contractures and pressure injuries temperature management and nutritional management especially to address the increases in resting energy expenditure and subsequent weight loss and we also want to prevent and treat issues like constipation and urinary retention as well as pain gabapentin has had some documented effects on presynaptic voltage-gated calcium channels in the dorsal horn of the spinal cord and it's been found to be clinically useful in patients with PSH who are unresponsive to beta blockers or bromocriptine I typically use gabapentin as an adjunct in PSH management especially to help with overall pain and discomfort the hope is with not only medications but miscellaneous interventions that treatment will help decrease comorbidities shorten hospital stays and then over improve overall patient outcomes I just want to touch a little bit on the differential diagnosis of things we should be considering outside of PSH because as we know PSH is a diagnosis of exclusion and some there are some diagnoses that can mimic some of these symptoms and we want to always rule out life-threatening illnesses first so the differential can be quite broad it can be something as simple as a urinary tract infection or pain dehydration or something more life-threatening like NMS or malignant hyperthermia what's important to note is that the timing of symptoms onset to a noxious stimuli possible improvement after correction of the noxious stimuli and then the combination of symptoms occurring together can all help you or help clue in on a PSH diagnosis can all help you or help clue in on a PSH diagnosis and then you can also use the diagnostic tools we discussed earlier in the presentation but you also should review the medications that the patient is on as some of those medications could be masking some of the symptoms and make the diagnosis a little bit more challenging. Neuroleptic malignant syndrome we would definitely want to make sure this is on our differential especially if patient has been given some things like Haldol or Reglan things that would differentiate it from PSH would be high fevers as well as elevated CK and muscle rigidity and then of course some of these medications that may have been recently added to their regimen. Malignant hyperthermia is also something to make sure you're aware of. It's where the skeletal muscle is characterized by hypermetabolism occurring with exposure to certain triggering agents most often inhalation anesthetics like succinylcholine. You can also see rhabdomyolysis renal and liver failure that develop and then they also have very high temperatures up to 44 degrees Celsius. One thing I found interesting was you can often observe it in their master muscles and then extremities and chest so it's something to keep in mind as far as their differential goes. Diencephalic seizures this was at one point thought to be what PSH was but for seizures of course they respond to AEDs but storming does not. For autonomic dysreflexia a lot of times this is something that can muddy the picture especially if there is a patient that you're managing that has a dual diagnosis of brain injury and spinal cord injury. This is typically for spinal cord injury patients above TA that are at risk of AED and removing the stimulus to relieve AED is definitely as important for that. Then you have central fever which also is a diagnosis of exclusion relatively resistant to any antipyretic treatment but again it could be very close to mimicking PSH and it's also something just to keep in mind. One thing that may help with differentiation is the absence of sweating especially if they do also have concurrent proximal sympathetic hyperactivity and then of course agitation. This is a clinical sign that's most often confused with PSH usually after emergence from true coma and you have a lack of autonomic instability so you don't have the temperature or blood pressure increases and that's what typically distinguishes it from storming. Something to keep in mind is also if they're undergoing an e-withdrawal and have subsequent agitation. This by no means was an exhaustive list but definitely ones that we should consider as far as the differential goes. I think one more question. So differential diagnoses of PSH include all of the following except okay let's see so yes opioid overdose right you'll have more of a decrease in sympathetic response but sepsis alcohol withdrawal and neuroleptic malignant syndrome are all diagnoses to keep in the differential. And then PSH has been shown to be associated with Yes, higher morbidity and mortality rates. It's longer hospital stays, decrease or not as much improvement in rehab, and then of course increased health care costs. So, like we talked about, the shorter the episodes of PSH, the better the outcome, the better response to empirical treatment, the better the outcome. We know PSH can worsen different clinical outcomes, such as the Glasgow Outcome Scale FIM scores, duration of PTA, increased hospital length of stay, both in ICU and rehab, and it also can lead to higher disability rating scores. All of this will subsequently lead to an additional burden on the healthcare system as they have a greater need for interventions. There's also the potential increase for secondary morbidity, like we talked about, the hypermetabolism with leading to body weight decrease and requiring feeding devices, higher prevalence of trachs, increased likelihood of complications such as HO in contractors, prolonged hypersympathetic tone has also been shown to lead to cardiac damage and immune suppression, and fluid loss from diaphoresis can also lead to downstream effects of hypernatremia, renal insufficiency, and thickened pulmonary secretions, and Pazzi et al. actually found that the occurrence of death to be almost tenfold in patients with PSH versus those without, and as we talked about, the average duration is very variable depending on the source and depending on whether it's an adult or child, but the more severe the brain injury, the higher the risk of prolonged dysautonomia, and overall, PSH is an independent risk factor for poor neurological outcomes in patients who have had an acquired brain injury, and being equipped with the knowledge on how to identify and treat PSH accordingly is ultimately and hopefully what's going to make for better patient outcomes in our patients who do survive severe brain injuries. I think that's it. Questions or even things to add about what you normally do at your institution? Amanda, you had used ITB. Is that what you said for one patient who was refracted to oral medications? Yes, we had one case where it was a 16-year-old with an anoxic injury, and we trialed many different medications, and he ultimately, we had told them, you have to be really careful. His heart rate's low when he's at rest, and he ultimately had a second cardiac arrest because of that, and so we didn't have much options, and so we had to use intrathecal baclofen. Did you have good results with the intrathecal? Yeah, I would say he had less storming episodes, and we were able to get him out of the ICU. That's awesome. Yeah, and to the point where he eventually went into rehab, but needed pretty high doses of intrathecal baclofen and rapid escalation of it as well. Yeah, it's just not something that's easily accessible or conducive, especially given the cost. Elizabeth asked, have you noted an increase in acute care providers calling everything PSH? Yes, everything is storming, which is why I'm passionate about PSH, because everything is not storming, so it just requires ongoing education, and so hopefully this presentation gave you guys some key things you can talk about with the acute care colleagues, but yes, everything is storming, which it should be the opposite, right? It's a diagnosis of exclusion, so everything else should be worked up and not just called storming or PSH. I recently had some success compromising and saying, let's give the antibiotics 48 hours. If we're still having fevers, then here's your plan, and that was helpful, but yeah, we come across that a lot. Yeah, it's all storming all the time. I'm like, well, I don't know if they've had a fever for 48 hours straight if that's the story. Yeah, yeah. Oh, Katie has an auto-text concerner. Let's see, maybe this will help with my consult notes. I do try to educate, because what ends up happening, right, it's usually the trainees that are calling you, the ICU residents, ICU fellows, the PD residents, and we have such a big institution that it's hard to provide that same education. Oh, she sent messages too long. Hold on, but we definitely try to educate of why we think it's storming or why, you know, why it's not storming. A lot of times we get patients who had an injury like a year ago, and they never really had any storming or paroxysmal sympathetic hyperactivity, but all of a sudden they're in for an infection, and they have worsening tone, but they always had tone, and everyone's like, oh, please come evaluate them for storming, but no, they really just need some tone management and some medication. Thanks, Raji. Any other tidbits you guys like to share about PSH or things you do at your institution? Sorry, go ahead, Vera. Oh, no worries. I just have a question, just kind of to understand how you think about it, because I understand that in my institution, usually we kind of think of different components of storming, and kind of you address tone separately, you address heart rate a little bit separately. Of course, it's all kind of overlapping issues, but kind of for tone and for, yeah, for tone, I see different approaches based on the age. I tend to see a little bit more benzos used during the first and second year, I think, here at Columbia, and less Baclofen. I understand that's due to the concern for GERD and kind of increased arching in them, just because that's been noted with Baclofen, but I was just wondering if that's also how you approach this, because it has been bothering me that we're giving those benzos to the little ones who we want to develop, and at the same time, we might be compromising their development, and I know it helps. I don't get it wrong. It helps with symptoms. The question is the outcomes. No, I think that's a great point. I'm also very hesitant to start any benzos. A lot of times, unfortunately, by the time they get us, there's already, you know, diazepam scheduled, or they've been using it for aborting some episodes. I try to avoid it as much as possible. I will use Baclofen in maybe a bigger one-year-old and two-year-old, but I also have found gabapentin to be underutilized, and the kids that I've seen after brain injury who have some posturing, some neuroirritability, they have responded pretty well overall to gabapentin, and it's not something that I'm, you know, worried that it's going to impair them or worsen their cognition, so gabapentin is something that I typically go to, and especially for the smaller kids, because I do try to avoid the benzos as much as possible, but again, it's a case-by-case basis, and that's a very valid point that the benzos can impact cognition negatively, and so you want to try to avoid that as much as possible. Understood. So then for someone who is, for example, I don't know, seven to eight months, for example, would you do clonidin and GABA to start, or propranolol and GABA to start? Yeah, so I typically look at what their vitals have been like and kind of graph those out and see, again, because I also don't want them to be dipping and bradycardic in between, so my go-to is typically propranolol. I find it easier to come off of, and it's easier to schedule PRNs in between scheduled propranolol, and then, yeah, GABA and or baclofen, just depending on the size of the child. And the benzo would be the last thing you would add on if you have to. Got it, okay, understood. Thank you, thanks for this wonderful lecture, so timely, so many of them. Katie, I like that. That's, I feel like I need to plug that into my consult note. That's a great, that's very long, but it's great. And then you've, I don't know how you could incorporate the table. You're talking about the management, the algorithm? Yeah, so I have it typed out with the citation, like I just have each, it's just too many words to paste into the, and then I delete the ones I'm not recommending. So if I'm recommending propranolol and baclofen, I'll keep those recommendations, or I'll delete the other drugs. No, that's awesome, because then whether now, whether the acute care teams read all of that, but I got to figure out a way to incorporate the table or the algorithm. I think there are some really good algorithms out there, but I definitely like the one for the Morozova paper. But any, I think we are over time, unless there's any other questions. All right, well thank you guys for participating, and please reach out if you have any other questions or comments. I do love talking about PSH. Thank you guys!

paroxysmal sympathetic hyperactivity

pediatric brain injuries

clinical manifestations

early diagnosis

medication management

non-pharmacological interventions

differential diagnosis

case study

management algorithms