I'd like to invite to the stage Dr. Derek Yeses, who will talk about ASL perfusion imaging of the frontal lobes predicts occurrence and resolution of posterior fossa syndrome, paper to be discussed by Dr. David Limbrick. Thank you. So I'd like to start by thanking the scientific committee for the opportunity to present our work here. I have no disclosures. So posterior fossa syndrome is a common complication of posterior fossa tumor surgery in children. There's a broad range of reported incidents in the literature, but it's around 20% following surgery in these kids. And the symptoms of posterior fossa syndrome are very wide ranging and go far beyond the canonical cerebellar symptoms. And while individual children can have a particular array of these, most children have mutism, ebulia, emotional disturbances, behavioral symptoms, as well as some more common cerebellar symptoms such as ataxia. And these children do almost always recover. However, there's been several studies which have come out recently suggesting that these children do have significantly worse long-term cognitive and psychosocial outcomes. And the pathophysiology of posterior fossa syndrome has generally been incompletely understood. So early series associated posterior fossa syndrome with damage to the vermis. And this led to a relatively widespread adoption of the telovilar approach for fourth ventricular tumors. However, later series of outcomes following surgical resection via the telovilar approach did not find any significant change in the incidence of posterior fossa syndrome, suggesting that damage to the vermis was probably not the causative factor. Later on, there were several radiologic studies which strongly associated posterior fossa syndrome with damage to the cerebellar e-parent pathways, most notably the dentate nuclei and the superior cerebellar peduncles, and especially when the damage was bilateral. This was also consistent with some data from some pioneers of functional neurosurgery who found that bilateral dentate lesioning could often lead to mutism. So I think these studies did a good job of identifying the site of injury in posterior fossa syndrome, which is most likely the cerebellar e-parent pathways, but they still don't explain the wide-ranging symptoms, which are more consistent with cortical dysfunction. This led several groups to propose the hypothesis of cerebellocerebral diascesis as the cause of posterior fossa syndrome. So what is diascesis? It's a disruption in brain function due to interruption at a remote site of a-parent input to that area. So in this case, the net excitatory input from the cerebellum to the cortex is being interrupted by damage to the e-parent pathways, leading to cortical dysfunction and lower activity. And there were several imaging studies which confirmed this hypothesis, using nuclear medicine approaches and dynamic susceptibility-weighted contrast MRI. And these are some representative images, and they show that the frontal lobes, as well as some other parts of cortex in these children, will have decreased perfusion or metabolism. And so I think these studies really confirm the hypothesis that cerebellocerebral diascesis is the underlying pathophysiology of posterior fossa syndrome. However, these imaging modalities are not practical for the widespread use in children. SPECT and PET scans require additional nuclear medicine studies, and dynamic susceptibility-weighted contrast MRI requires high contrast loads, large varieties, and it provides non-quantitative data that's difficult to compare across patients. Thankfully, there is an imaging modality that does not have these drawbacks, and that's arterial spin labeling perfusion imaging. And so I'll briefly describe what ASL imaging is. Using radio frequency pulses across a magnetic gradient, we can magnetically label the water molecules in the blood of the arteries in the neck, and then allow a labeling delay for this endogenous magnetic contrast agent to then label the, to then perfuse into the brain, and then we can detect that endogenous tracer. And we can repeat this several times and compare it to the pre-labeling imaging to get quantitative perfusion-weighted imaging. And this has several advantages, especially for the use in children. It requires no exogenous contrast agents, it provides quantitative, highly reproducible data across subjects, and it's relatively fast, it can be done in about five minutes, and it can be done with any commercially available MRI scanner. But it does have a few drawbacks, it's highly sensitive to motion, so in children this will generally restrict us to anesthetized scans. And it's difficult to do well without a 3T magnet. And at Stanford we had a somewhat unique opportunity to investigate ASL imaging in posterior faucet syndrome because we've been doing ASL imaging in most of our MRIs for the last several years. So for this study we did a retrospective chart review of pediatric brain tumor patients who were treated at Stanford from 2004 to 2016, and patients with posterior faucet syndrome were identified based on notes in the electronic medical record. We identified 11 patients with definite posterior faucet syndrome and four patients with probable posterior faucet syndrome for further analysis. We then compared the post-operative ASL imaging in the patients who went on to develop posterior faucet syndrome to patients who had medulloblastoma resections who did not go on to develop posterior faucet syndrome. And our institutional practice has been to keep the children intubated and sedated following surgery and obtain the post-operative MRI on post-operative day one prior to extubation. We also compared the post-operative ASL imaging in children with posterior faucet syndrome to their ASL imaging following the resolution of their symptoms, and we used resumption of speech as the marker for that. In this series all scans were obtained under general anesthesia on a 3T magnet. So when we compared the post-operative imaging in children who went on to develop posterior faucet syndrome to children who did not, we found statistically significant decreases in right frontal lobe perfusion and a trend towards decreased left frontal lobe perfusion. And we chose to analyze the frontal lobes because that had been suggested as the source of dysfunction in prior studies. And this remained significant after controlling for age and gender based on multivariate analysis. And these are some representative images showing the decreased perfusion in the children who went on to develop posterior faucet syndrome compared to children who had medulloblastoma resections who did not develop posterior faucet syndrome. When we looked at the ASL imaging from after resection, sorry, after resolution of posterior faucet syndrome symptoms compared to the post-operative imaging, we found significant increases in right and left frontal lobe perfusion after the recovery of symptoms. The analysis here includes both the certain and the probable mutism cases. When we restricted it to only the definite mutism cases, the right frontal lobe perfusion remained significant. However, the left fell below our a priori significance threshold. So this definitely has some limitations. It's retrospective. The sample size is small. And it's unclear if the results would be generalizable to a 1.5T magnet. So we've shown that we can use ASL perfusion to detect decreases in frontal lobe perfusion in children who will go on to develop posterior faucet syndrome. And that the resolution of these ASL perfusion abnormalities correlates with the resolution of posterior faucet syndrome symptoms. These data support the theory of cerebellosclerical diaschesis as the underlying pathophysiology of posterior faucet syndrome. And we think that in the future, pediatric neurosurgeons might be able to use post-operative ASL imaging to identify which patients are going to go on to develop posterior faucet syndrome and counsel families appropriately. Also as I mentioned at the beginning, there's an increasing appreciation that children with posterior faucet syndrome go on to have significantly worse long-term cognitive outcomes. And there's increasing momentum behind the idea that we should be considering treatments for these children to try to alleviate their posterior faucet syndrome to see if that can help with those cognitive outcomes. And we think ASL perfusion may be a useful imaging biomarker in those investigations. So I'd like to thank our patients and their families. Kristen Yeom is a pediatric neuroradiologist I work closely with on this project, as well as Katie, who's an excellent medical student who we worked with on this project. And my pediatric neurosurgery mentors, Dr. Grant, Dr. Edwards, Dr. Cheshire, and Dr. Hong. Thank you. All right, well, thank you. I'm just going to discuss Dr. Yisi's paper. Posterior faucet syndrome occurs in up to 39% of posterior faucet tumor resections. Just as cerebellar mutism or speech apraxia is also associated with myriad neurobehavioral and motor findings. The pathophysiology of this, of course, remains unclear. But it's important. Posterior faucet syndrome is associated with adverse cognitive outcomes and permanent problems like dysarthria, speech, emotional, and behavioral problems. And this is set at odds with our goal of maximal resection, where posterior faucet tumor resection confers survival advantage. The current study is a retrospective study of 15 patients with definite or probable posterior faucet syndrome. And the authors used arterial spin labeling, MR perfusion, to assess cortical blood flow in patients immediately after surgery who were then found to go on to develop posterior faucet syndrome. And these were compared with patients who had medulloblastoma resection, but ultimately did not develop posterior faucet syndrome. As a second step, they looked at the patients who did develop posterior faucet syndrome in their follow-up study upon return to speech. The authors found decreased right frontal lobe perfusion and a trend towards decreased left frontal lobe perfusion compared with medulloblastoma patients without posterior faucet syndrome. And they also showed that patients with posterior faucet syndrome showed increased perfusion both in the right and left frontal lobes following return to speech. Of course, this is a pilot study with a modest sample size, and the authors did adjust for sex and age, but there are a number of other important factors such as brain tumor pathology, histology, location, and hydrocephalus that were not adjusted for. The regions of interest were large and rather arbitrarily selected, nonspecific. And it's important to point out that arterial spin labeling is sensitive to susceptibility in motion artifact, and additional analyses have to be done to account for blood T1 products in children of age and hematocrit matching. This is an innovative study. Arterial spin labeling is broadly available and easily available to support clinical protocols, standard clinical protocols, and no contrast is required. Also, they can be quantitated across subjects. The biggest impact of this study is that it provides supportive evidence for the cerebellocerebral diascesis notion, and by which injury to the proximal cerebellar efferents affect the dentata rubrothalamic cortical pathway, with loss of cerebellar input and consequent reduction in supratentorial perfusion metabolism and widespread cortical dysfunction. The authors should be congratulated for this innovative and impactful study. Thank you.

ASL perfusion imaging

frontal lobes

posterior fossa syndrome

PFS

cerebellocerebral diaschesis