Four cases of acute comitant esotropia associated with diffuse intrinsic pontine glioma in children.

BACKGROUND: Acute acquired concomitant esotropia (AACE) is usually a benign form of strabismus that infrequently is associated with intracranial pathology. Clinicians have noted an increase in its incidence and theorize that it may be related to public health "lockdown" measures taken in response to the COVID-19 pandemic. With an increased incidence of AACE clinicians must firstly differentiate AACE from common accommodative esotropia and secondly recognize AACE as a possible sign of serious neuropathology.Diffuse Intrinsic Pontine Glioma (DIPG) is a devastating diagnosis for affected families. Children typically present at age 6-7 years with cranial nerve palsies, long tract signs, and/or cerebellar signs. Diagnosis is made from characteristic findings on magnetic resonance brain imaging (MRI brain) and treatment includes radiotherapy and palliative care. Two years from diagnosis, 90% of affected children will have died from their disease. CASE SERIES: We present four cases that attended our pediatric ophthalmology clinic with AACE either as a presenting sign of DIPG or as a clinical finding following a DIPG diagnosis. Patient A (age 5 years) presented to the emergency eye clinic with sudden onset diplopia and intermittent esotropia. Suppression later developed, they had 0.00 logMAR visual acuity either eye, and bilateral physiological hypermetropia. MRI brain imaging requested as a result of the unusual presentation led to the DIPG diagnosis. The other 3 cases (ages 11, 5 & 5 years) were assessed post DIPG diagnosis and found to have an esotropia measuring bigger on 1/3-meter fixation than 6-meter fixation, full ocular motility, physiological hypermetropia or emmetropia, and visual acuity normal for age. Other than patient B (age 11 years), who had papilledema and gaze evoked nystagmus when they were assessed 2 weeks prior to death, no patient had any other clinical eye findings. CONCLUSIONS: This small series of 4 patients attending our clinic within a 12-month period supports the notion that children presenting with AACE should routinely be offered brain MRI. Not all children with DIPG-associated AACE have significant ophthalmic findings indicative of intracranial pathology. With the potential for increased incidence of AACE related to lockdowns, clinicians should be reminded of the infrequent possibility their patient has a more serious condition.

High Prevalence of Developmental Venous Anomaly in Diffuse Intrinsic Pontine Gliomas: A Pediatric Control Study.

BACKGROUND: No link has been demonstrated between diffuse intrinsic pontine glioma and developmental venous anomaly in pediatric patients. OBJECTIVE: To determine the prevalence of developmental venous anomaly in a pediatric cohort of diffuse intrinsic pontine glioma. METHODS: We performed a retrospective cohort study (1998-2017) of consecutive pediatric patients harboring a diffuse intrinsic pontine glioma (experimental set, n = 162) or a craniopharyngioma (control set, n = 142) in a tertiary pediatric neurosurgical center. The inclusion criteria were the following: age <18 yr at diagnosis; histopathological diagnosis of diffuse intrinsic pontine glioma or craniopharyngioma according to the 2016 World Health Organization classification of tumors of the central nervous system; no previous oncological treatment; and available preoperative magnetic resonance imaging performed with similar acquisition protocol. RESULTS: We found a significantly higher prevalence of developmental venous anomaly in the experimental set of 162 diffuse intrinsic pontine gliomas (24.1%) than in the control set of 142 craniopharyngiomas (10.6%; P = .001). The prevalence of developmental venous anomalies was not significantly impacted by demographic data (sex, age at diagnosis, and underlying pathological condition), biomolecular analysis (H3-K27M-mutant subgroup, H3.1-K27M-mutant subgroup, and H3.3-K27M-mutant subgroup), or imaging findings (anatomic location, anatomic extension, side, and obstructive hydrocephalus) of the studied diffuse intrinsic pontine gliomas. CONCLUSION: We report a higher prevalence of developmental venous anomaly in pediatric diffuse intrinsic pontine glioma patients than in control patients, which suggests a potential underlying common predisposition or a causal relationship that will require deeper investigations.

Delta-24-RGD combined with radiotherapy exerts a potent antitumor effect in diffuse intrinsic pontine glioma and pediatric high grade glioma models.

Pediatric high grade gliomas (pHGG), including diffuse intrinsic pontine gliomas (DIPGs), are aggressive tumors with a dismal outcome. Radiotherapy (RT) is part of the standard of care of these tumors; however, radiotherapy only leads to a transient clinical improvement. Delta-24-RGD is a genetically engineered tumor-selective adenovirus that has shown safety and clinical efficacy in adults with recurrent gliomas. In this work, we evaluated the feasibility, safety and therapeutic efficacy of Delta-24-RGD in combination with radiotherapy in pHGGs and DIPGs models. Our results showed that the combination of Delta-24-RGD with radiotherapy was feasible and resulted in a synergistic anti-glioma effect in vitro and in vivo in pHGG and DIPG models. Interestingly, Delta-24-RGD treatment led to the downregulation of relevant DNA damage repair proteins, further sensitizing tumors cells to the effect of radiotherapy. Additionally, Delta-24-RGD/radiotherapy treatment significantly increased the trafficking of immune cells (CD3, CD4+ and CD8+) to the tumor niche compared with single treatments. In summary, administration of the Delta-24-RGD/radiotherapy combination to pHGG and DIPG models is safe and significantly increases the overall survival of mice bearing these tumors. Our data offer a rationale for the combination Delta-24-RGD/radiotherapy as a therapeutic option for children with these tumors. SIGNIFICANCE: Delta-24-RGD/radiotherapy administration is safe and significantly increases the survival of treated mice. These positive data underscore the urge to translate this approach to the clinical treatment of children with pHGG and DIPGs.