CNTM-06. Individual Cerebrocerebellar Functional Network Analysis for Decoding the Symptomatological Dynamics of Posterior Fossa Syndrome

Posterior fossa syndrome (PFS) consists of three types of symptom (motoric, linguistic, and neurobehavioral) in patients with posterior fossa pathologies. The evolutional mechanism of this high cognitive syndromic complex from cerebellar origin remains unconfirmed. Previous studies analyzing PFS patients mostly focused on the association between structural abnormalities that occur during PFS, of which proximal efferent cerebellar pathway (pECP) injury appears to be the most common pathogenesis. However, structural imaging may not be sensitive enough to determine the dynamic course of PFS, since the symptomatology is primarily an output of cerebral operation. On the other hand, a network neuroscience approach using a mathematical model to extract information from functional imaging to generate interregional connectivity provides abundant evidence that the cerebellum is influential in modulating cerebral functions. This study applied a network approach to children with PFS. Scaling of each symptom domain was used to quantify the dynamics of the syndrome. An individual cerebrocerebellar functional network analysis was then performed to determine the network dynamics during PFS. Cross-validation of clinical neurophysiology and functional neuroscience suggested the critical role of the pECP within PFS from the network analysis. The employed approach was therefore useful in determining the complex clinical symptoms using individual functional network analysis, which bridges the gap between structural neuroimaging and clinical neurophysiology.

QOL-28. NEUROCOGNITIVE PROFILE OF PEDIATRIC MEDULLOBLASTOMA PATIENTS PRIOR TO RADIATION THERAPY

Neurocognitive late effects are unfortunately common following treatment for pediatric medulloblastoma. While radiation therapy is an essential component of treatment for most pediatric medulloblastoma patients, it is associated with neurocognitive compromise. Effects include deficits in cognitive speed and performance efficiency, aspects of attention, as well as working memory. Yet long after treatment it is difficult to tease apart relative contributions of other risk factors to neurocognitive functioning beyond radiation. We examined neurocognitive functioning in a sample of pediatric medulloblastoma patients prior to radiation therapy, including investigation of neurocognitive risk factors such as hydrocephalus, presence of posterior fossa syndrome, and duration of neurological symptoms prior to diagnosis. Results indicated that the sample functioned in the average range in terms of overall IQ (n=34, X̅=103). Patients also functioned in the normal range in terms of language-based ability (X̅=106), nonverbal ability (X̅=104), and working memory (X̅=103). However, the sample performed statistically significantly lower than the general population in terms of cognitive speed and efficiency (z=-2.026, p=.043). The sample was also rated by parents as exhibiting more attention problems relative to the general population (z=1.988, p=.047). There was no specific association with hydrocephalus, duration of symptoms, or history of posterior fossa syndrome. Results suggest weaknesses in attention and processing speed may exist in some pediatric medulloblastoma patients prior to radiation therapy secondary to tumor and related complications. Implications for future research are presented, along with difficulties inherent to “baseline” assessment with pediatric brain tumor survivors.

NCMP-25. CLINICAL FEATURES, NEUROLOGIC RECOVERY, AND RISK PREDICTION OF POST-OPERATIVE POSTERIOR FOSSA SYNDROME: A PROSPECTIVE STUDY

INTRODUCTION Posterior fossa syndrome (PFS) is a known consequence of medulloblastoma resection. Our aim was to clinically define PFS, its evolution over time, and ascertain risk factors for its development and poor recovery. METHODS Children with medulloblastoma treated at St Jude Children’s Research Hospital from 6/2013-7/2019 received standardized neurological examinations, before and periodically after radiation therapy. Most (98.3%) were enrolled on the ongoing multi-institutional protocol (SJMB12; NCT 01878617). RESULTS Sixty (34%) of 178 evaluated children had PFS. Forty (23%) had complete mutism (PFS1) and 20 (11%) had diminished speech (PFS2). All children with PFS had severe ataxia and 42.5% of PFS1 had movement disorders. By multivariable analysis, younger age (p=0.0005) and surgery in a low-volume surgery center (p=0.0146) increased PFS risk, while SHH tumors had reduced risk (p=0.0025). Speech and gait returned in PFS1/PFS2 children at a median of 2.3/0.7 and 2.1/1.5 months respectively, however, 12 (44.4%) of 27 PFS1 children with 12 months of follow-up were non-ambulatory at one-year. Movement disorder (p= 0.037) and high ataxia score (p< 0.0001) were associated with delayed speech recovery. Older age (p= 0.0147) and high ataxia score (p< 0.0001) were association with delayed gait return. Symptoms improved in all children but no child with PFS had normal neurologic examination at a median of 23 months after surgery. CONCLUSION Categorizing PFS in to types 1 and 2 has prognostic relevance. Almost half of the children with PFS1 remained non-ambulatory at 12-month follow-up. Surgical experience was a major modifiable contributor to the development of PFS.

Arterial spin labeling perfusion changes of the frontal lobes in children with posterior fossa syndrome

OBJECTIVEPosterior fossa syndrome (PFS) is a common complication following the resection of posterior fossa tumors in children. The pathophysiology of PFS remains incompletely elucidated; however, the wide-ranging symptoms of PFS suggest the possibility of widespread cortical dysfunction. In this study, the authors utilized arterial spin labeling (ASL), an MR perfusion modality that provides quantitative measurements of cerebral blood flow without the use of intravenous contrast, to assess cortical blood flow in patients with PFS.METHODSA database of medulloblastoma treated at the authors’ institution from 2004 to 2016 was retrospectively reviewed, and 14 patients with PFS were identified. Immediate postoperative ASL for patients with PFS and medulloblastoma patients who did not develop PFS were compared. Additionally, in patients with PFS, ASL following the return of speech was compared with immediate postoperative ASL.RESULTSOn immediate postoperative ASL, patients who subsequently developed PFS had statistically significant decreases in right frontal lobe perfusion and a trend toward decreased perfusion in the left frontal lobe compared with controls. Patients with PFS had statistically significant increases in bilateral frontal lobe perfusion after the resolution of symptoms compared with their immediate postoperative imaging findings.CONCLUSIONSASL perfusion imaging identifies decreased frontal lobe blood flow as a strong physiological correlate of PFS that is consistent with the symptomatology of PFS. This is the first study to demonstrate that decreases in frontal lobe perfusion are present in the immediate postoperative period and resolve with the resolution of symptoms, suggesting a physiological explanation for the transient symptoms of PFS.

Predictors of Posterior Fossa Syndrome: Results From an International Multicenter Cohort Study of Molecularly Characterized Medulloblastoma Patients

INTRODUCTION Posterior Fossa Syndrome (PFS) is a common complication following surgical resection of pediatric posterior fossa tumors. PFS is characterized by a combination of mutism, ataxia, and other behavioral symptoms that typically improves within weeks to months. Medulloblastoma histology, midline location, and brainstem invasion increase risk for PFS. Medulloblastoma subgroups have historically been treated as a single entity when assessing PFS risk, however, recent studies highlighting their clinical heterogeneity suggest the need for a subgroup-specific analysis of PFS risk. Here, we examine a large international multicenter cohort of molecularly characterized medulloblastoma patients to assess predictors of PFS. METHODS We assembled a cohort of 270 medulloblastoma patients from 4 sites including Christian Medical College and Hospital (n = 87), Great Ormond Street Hospital (n = 25), Hospital for Sick Kids (n = 111), and Stanford University Medical Center (n = 47), who underwent surgical treatment of medulloblastoma and had molecular subgrouping of their tumors. Patient age at diagnosis, gender, tumor volume, and PFS status were assessed in addition to molecular subgroup. RESULTS Overall, 25.9% of our cohort developed PFS. PFS patients were younger (mean difference −2.73 yr ± 0.8, P = .0009) and had larger tumors (mean difference 16.99 cm3 ± 5.287, P = .0015) that were more midline (OR = 20.03, P < .0001). On multivariate analysis adjusting for age, sex, midline location, and tumor volume, WNT (adjusted OR = 5.19, P = .022) and Group 4 (adjusted OR = 7.15, P = .004) tumors were found to be independently associated with higher risk of PFS as compared to SHH tumors. CONCLUSION Here, we present the largest molecularly characterized cohort of medulloblastoma patients in the context of PFS development. In combination with recent data showing that WNT and Group 4 tumors have a longer pre-diagnostic interval our results support the hypothesis that large midline tumors that grow slowly have a higher risk of PFS.