Modern Radiation Treatment Planning Parameters and Outcomes in Pediatric Tectal Gliomas.

Purpose: Pediatric low-grade tectal gliomas are rare, indolent tumors of the brain stem. We reviewed outcomes of pediatric patients who received a diagnosis of low-grade tectal gliomas and report dosimetric parameters for those receiving radiation therapy (RT). Methods and Materials: We retrospectively reviewed all pediatric patients (age <18 years) at our institution diagnosed with a low-grade glioma between 1993 and 2020 (n = 288). Twenty-three patients with tectal gliomas were identified. Patients who received RT (n = 8) had detailed dosimetric analyses performed. Doses to critical structures and any resulting toxicities were reviewed. Minimum follow-up was 2 years and complete follow-up was available for all patients. Results: Twenty-three patients, with a median age of 8.9 years, were included (range, 0.5-16.2 years). At a median follow-up of 7.4 years (range, 2-24 years), all were alive at the end of the study period. Three patients (13%) were treated with upfront RT; none of these patients developed local failure (LF) after a median follow-up of 10.6 years. One patient was treated with upfront chemotherapy with no evidence of progression afterward. Nineteen patients were initially observed after diagnosis and 26% of them (n = 5) experienced local progression. All 5 were treated with salvage RT, with 1 patient requiring further treatment with chemotherapy. Fractionation schedules for patients undergoing upfront or salvage RT included 50.4 Gy in 28 fractions (n = 4), 54 Gy in 30 fractions (n = 2), and 51 Gy in 30 fractions (n = 2). For patients treated after 2007, the gross tumor volume was delineated on a T2 magnetic resonance imaging with an average gross tumor volume-to-planning target volume expansion of 4.5 mm (range, 3-5 mm). Detailed dosimetric parameters were available for all patients treated with RT. Conclusions: Our review supports the indolent behavior for most tectal gliomas. For the subset of tumors with evidence of progression, modern photon RT results in excellent oncologic outcomes with minimal late effects.

Neuroanatomy of Cerebellar Mutism Syndrome: The Role of Lesion Location.

Approximately 25% of pediatric patients who undergo cerebellar tumor resection develop cerebellar mutism syndrome (CMS). Our group recently showed that damage to the cerebellar deep nuclei and superior cerebellar peduncles, which we refer to as the cerebellar outflow pathway, is associated with increased risk of CMS. Here, we tested whether these findings replicate in an independent cohort. We evaluated the relationship between lesion location and the development of CMS in an observational study of 56 pediatric patients who underwent cerebellar tumor resection. We hypothesized that individuals that developed CMS after surgery (CMS+), relative to those that did not (CMS-) would have lesions that preferentially intersected with: 1) the cerebellar outflow pathway, and 2) a previously generated 'lesion-symptom map' of CMS. Analyses were conducted in accordance with pre-registered hypotheses and analytic methods (https://osf.io/r8yjv/). We found supporting evidence for both hypotheses. Compared with CMS- patients, CMS + patients (n = 10) had lesions with greater overlap with the cerebellar outflow pathway (Cohen's d = .73, p = .05), and the CMS lesion-symptom map (Cohen's d = 1.1, p = .004). These results strengthen the association of lesion location with risk of developing CMS and demonstrate generalizability across cohorts. These findings may help to inform the optimal surgical approach to pediatric cerebellar tumors.

Characterizing academic performance in pediatric acute lymphoblastic leukemia with population-based achievement tests.

BACKGROUND: Recent shifts from radiation to chemotherapy-based treatment for acute lymphoblastic leukemia (ALL) have contributed to reduced long-term morbidity. Despite this, ALL survivors remain at increased risk for long-term cognitive impairments. AIM: To identify demographic and treatment factors associated with school performance in pediatric survivors of ALL. METHODS: We collected standardized test scores for reading, math, and science obtained in a school setting from grades 3-11 in 63 ALL survivors (46.0% boys). Most participants were assessed across multiple grades (median number of grades n = 5, range 1-7), and 269 observations were considered in the analyses. Treatment exposures were extracted from medical records. Socio-economic status was estimated using participation in free/reduced lunch programs at school. Mixed effects linear regression models were conducted to determine factors associated with school performance. RESULTS: ALL survivors' scores were comparable to state norms on reading, math, and science performances. On multivariable analysis, participation in free/reduced lunch programs was significantly associated with lower reading scores (ß = -12.52; 95% CI -22.26:-2.77, p = .01). Exposure to radiation during treatment was also associated with lower reading test scores (ß = -30.81, 95% CI -52.00:-9.62, p = .01). No significant associations between demographics and treatment parameters were observed for math and science test scores. CONCLUSIONS: We utilized population-based achievement tests conducted from grades 3-11 to characterize school performance in ALL survivors. Our results imply that survivors with low socio-economic status and those exposed to radiation during treatment could benefit from early monitoring and intervention to maximize academic success.

Habituation of parasympathetic-mediated heart rate responses to recurring acoustic startle.

Startle habituation is a type of implicit and automatic emotion regulation. Diminished startle habituation is linked to several psychiatric or neurological disorders. Most previous studies quantified startle habituation by assessing skin conductance response (SCR; reflecting sympathetic-mediated sweating), eye-blink reflex, or motor response. The habituation of parasympathetic-mediated heart rate responses to recurrent startle stimuli is not well understood. A variety of methods and metrics have been used to quantify parasympathetic activity and its effects on the heart. We hypothesized that these different measures reflect unique psychological and physiological processes that may habituate differently during repeated startle stimuli. We measured cardiac inter-beat intervals (IBIs) to recurring acoustic startle probes in 75 eight year old children. Eight acoustic stimuli of 500 ms duration were introduced at intervals of 15-25 s. Indices of parasympathetic effect included: (1) the initial rapid decrease in IBI post-startle mediated by parasympathetic inhibition (PI); (2) the subsequent IBI recovery mediated by parasympathetic reactivation (PR); (3) rapid, beat-to-beat heart rate variability (HRV) measured from the first seven IBIs following each startle probe. SCR and motor responses to startle were also measured. Results showed that habituation of PR (IBI recovery and overshoot) and SCRs were rapid and robust. In addition, changes in PR and SCR were significantly correlated. In contrast, habituation of PI (the initial decrease in IBI) was slower and relatively modest. Measurement of rapid HRV provided an index reflecting the combination of PI and PR. We conclude that different measures of parasympathetic-mediated heart rate responses to repeated startle probes habituate in a differential manner.

Manipulative and antisocial behavior in an 11-year-old boy with epilepsy.

Brian is an 11-year-old boy who presented to the emergency room with suicidal ideation and hearing voices. In the preceding weeks, he had escalating symptoms of oppositional defiant disorder, attention-deficit hyperactivity disorder (ADHD), and bipolar disorder. His medical history was notable for complex partial epilepsy with onset at age 4 that had been well controlled with divalproate. He had several mental health diagnoses by various practitioners including oppositional defiant disorder, ADHD, and bipolar disorder. Brian's family and social history was notable for the absence of identifiable risk factors for seizures or psychiatric problems. Over the course of a week-long psychiatric hospitalization, his complaints of depression and hearing voices seemed incongruent with his behavior. His parents endorsed a long history of Brian manipulating family and friends, such as conning his friends into stealing money and giving it to him. There was increasing suspicion that Brian was contriving his presenting symptoms for secondary gains. When his parents visited, he consistently bargained for prized items such as a long sought after cell phone and his own bedroom to improve his mood. His prior diagnoses (ADHD, a mood disorder, and oppositional defiant disorder) did not capture what seemed to be his core problem--an ability and willingness to manipulate others for his own self-serving purposes. Three months later, he was seen in the pediatric neurology clinic for increased seizure frequency. In the interim, he had several very serious altercations including setting fire to his family church, an attempted break-in-and-entry, assaulting his principal and resisting the arresting officer, and a malicious planned attack on his father where he struck him in the head with a crescent wrench "in cold blood, without any emotion."

Behavioral effects of congenital ventromedial prefrontal cortex malformation.

BACKGROUND: A detailed behavioral profile associated with focal congenital malformation of the ventromedial prefrontal cortex (vmPFC) has not been reported previously. Here we describe a 14 year-old boy, B.W., with neurological and psychiatric sequelae stemming from focal cortical malformation of the left vmPFC. CASE PRESENTATION: B.W.'s behavior has been characterized through extensive review Patience of clinical and personal records along with behavioral and neuropsychological testing. A central feature of the behavioral profile is severe antisocial behavior. He is aggressive, manipulative, and callous; features consistent with psychopathy. Other problems include: egocentricity, impulsivity, hyperactivity, lack of empathy, lack of respect for authority, impaired moral judgment, an inability to plan ahead, and poor frustration tolerance. CONCLUSIONS: The vmPFC has a profound contribution to the development of human prosocial behavior. B.W. demonstrates how a congenital lesion to this cortical region severely disrupts this process.