Eye Movements and White Matter are Associated with Emotional Control in Children Treated for Brain Tumors.

OBJECTIVE: Children treated for brain tumors often experience social and emotional difficulties, including challenges with emotion regulation; our goal was to investigate the attention-related component processes of emotion regulation, using a novel eye-tracking measure, and to evaluate its relations with emotional functioning and white matter (WM) organization. METHOD: Fifty-four children participated in this study; 36 children treated for posterior fossa tumors, and 18 typically developing children. Participants completed two versions of an emotion regulation eye-tracking task, designed to differentiate between implicit (i.e., automatic) and explicit (i.e., voluntary) subprocesses. The Emotional Control scale from the Behavior Rating Inventory of Executive Function was used to evaluate emotional control in daily life, and WM organization was assessed with diffusion tensor imaging. RESULTS: We found that emotional faces captured attention across all groups (F(1,51) = 32.18, p < .001, η2p = .39). However, unlike typically developing children, patients were unable to override the attentional capture of emotional faces when instructed to (emotional face-by-group interaction: F(2,51) = 5.58, p = .006, η2p = .18). Across all children, our eye-tracking measure of emotion regulation was modestly associated with the parent-report emotional control score (r = .29, p = .045), and in patients it was associated with WM microstructure in the body and splenium of the corpus callosum (all t > 3.03, all p < .05). CONCLUSIONS: Our findings suggest that an attention-related component process of emotion regulation is disrupted in children treated for brain tumors, and that it may relate to their emotional difficulties and WM organization. This work provides a foundation for future theoretical and mechanistic investigations of emotional difficulties in brain tumor survivors.

Posterior fossa syndrome: Review of the behavioral and emotional aspects in pediatric cancer patients.

Medulloblastoma, the most common malignant brain tumor of childhood, occurs in the posterior fossa, the part of the intracranial cavity that contains the brainstem and the cerebellum. The cerebellum is involved in many complex aspects of human behavior and function, and when it is disrupted or insulted, this can lead to significant sequelae in children with posterior fossa tumors. A constellation of impairing and distressing symptoms, including mutism, ataxia/hypotonia, and emotional lability, develops in approximately 25% of children after the surgical resection of posterior fossa tumors. These symptoms may impede treatment and frequently require intervention in order for children to be able to participate in their care. The eventual recovery of speech occurs for most, but with slowly improving dysarthria over many months. Behavioral changes and emotional lability also occur. This phenomenon has been classified differently by different investigators over the past 35 years. For the purposes of this article, the term posterior fossa syndrome is used to refer to the neuropsychiatric and behavioral features that compose this condition. The current review summarizes the development of the clinical understanding of this phenomenon with a focus on near- and long-term psychosocial and psychiatric implications. Also, clinical examples of the presentation, management, and lasting implications of this syndrome are provided. This review is intended to be a resource for clinicians who treat affected children. Cancer 2017;123:551-559. © 2016 American Cancer Society.

Brain Perfusion and Diffusion Abnormalities in Children Treated for Posterior Fossa Brain Tumors.

OBJECTIVE: To compare cerebral perfusion and diffusion in survivors of childhood posterior fossa brain tumor with neurologically normal controls and correlate differences with cognitive dysfunction. STUDY DESIGN: We analyzed retrospectively arterial spin-labeled cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) in 21 patients with medulloblastoma (MB), 18 patients with pilocytic astrocytoma (PA), and 64 neurologically normal children. We generated ANCOVA models to evaluate treatment effects on the cerebral cortex, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, and cerebral white matter at time points an average of 5.7 years after original diagnosis. A retrospective review of patient charts identified 12 patients with neurocognitive data and in whom the relationship between IQ and magnetic resonance imaging variables was assessed for each brain structure. RESULTS: Patients with MB (all treated with surgery, chemotherapy, and radiation) had significantly lower global CBF relative to controls (10%-23% lower, varying by anatomic region, all adjusted P?

Cerebellar mutism syndrome in children with brain tumours of the posterior fossa.

BACKGROUND: Central nervous system tumours constitute 25% of all childhood cancers; more than half are located in the posterior fossa and surgery is usually part of therapy. One of the most disabling late effects of posterior fossa tumour surgery is the cerebellar mutism syndrome (CMS) which has been reported in up to 39% of the patients but the exact incidence is uncertain since milder cases may be unrecognized. Recovery is usually incomplete. Reported risk factors are tumour type, midline location and brainstem involvement, but the exact aetiology, surgical and other risk factors, the clinical course and strategies for prevention and treatment are yet to be determined. METHODS: This observational, prospective, multicentre study will include 500 children with posterior fossa tumours. It opened late 2014 with participation from 20 Nordic and Baltic centres. From 2016, five British centres and four Dutch centres will join with a total annual accrual of 130 patients. Three other major European centres are invited to join from 2016/17. Follow-up will run for 12 months after inclusion of the last patient. All patients are treated according to local practice. Clinical data are collected through standardized online registration at pre-determined time points pre- and postoperatively. Neurological status and speech functions are examined pre-operatively and postoperatively at 1-4 weeks, 2 and 12 months. Pre- and postoperative speech samples are recorded and analysed. Imaging will be reviewed centrally. Pathology is classified according to the 2007 WHO system. Germline DNA will be collected from all patients for associations between CMS characteristics and host genome variants including pathway profiles. DISCUSSION: Through prospective and detailed collection of information on 1) differences in incidence and clinical course of CMS for different patient and tumour characteristics, 2) standardized surgical data and their association with CMS, 3) diversities and results of other therapeutic interventions, and 4) the role of host genome variants, we aim to achieve a better understanding of risk factors for and the clinical course of CMS - with the ultimate goal of defining strategies for prevention and treatment of this severely disabling condition. TRIAL REGISTRATION: Clinicaltrials.gov : NCT02300766 , date of registration: November 21, 2014.

[VEGETATIVE REACTIONS AS PROGNOSTIC FACTOR IN POSTERIOR FOSSA SURGERY].

Mortality rate related to posterior fossa tumors resection varies from 1 to 8 percent, according to various authors. It depends on tumor size and its growth characteristics. To determine the physiological acceptability of surgery, physiological significance of vegetative reactions associated with tumors resection has to be assessed. We divide these reactions (centrogenic reactions - CR) into 2 main groups. The first group has a relatively precise morphofunctional structure, similar to the classic reflex arc. They appear due to irritation of local centers or cranial nerves nuclei with mixed motor-vegetative structure. In most cases they are not connected with anatomic damage of CNS structures. The second group of CR is correlated with dysfunction of brain and represents brain s attempt to turn into a new functional state. Their presence should be considered as a functional degradation symptom, which might be even irreversible. Emergence from anesthesia in the operative room is not recommended in this clinical situation. Neurovegetative stabilization should be provided for a period of 6 to 24 hours after tumor resection.

Pediatric posterior fossa ganglioglioma: unique MRI features and correlation with BRAF V600E mutation status.

Ganglioglioma (GG) is a rare pediatric brain tumor (1-4 %) with neoplastic glial and neuronal cells. Posterior fossa GGs (PF GGs) occur less frequently than supratentorial GGs (ST GGs). The BRAF V600E mutation has been reported in GGs and carries therapeutic implications. We compare the presenting symptoms, magnetic resonance imaging, BRAF V600E mutation status, treatment, and prognosis in children with ST and PF GGs. The neuro-oncology database at a tertiary care Children's Hospital was retrospectively reviewed from 1995 to 2010 for patients with ST and PF GG. All available imaging was reviewed. Symptoms, BRAF V600E mutation status, treatment, and survival data were collected from the electronic medical record and analyzed. Our series consisted of 11 PF GG and 20 ST GG. Children with PF GG presented with ataxia, cranial nerve deficits and long tract signs whereas the majority with ST GGs presented with seizures. On imaging, PF GGs were infiltrative and expansile solid masses with dorsal predominant "paintbrush" enhancement whereas ST GGs were well circumscribed mixed solid and cystic masses with heterogeneous enhancement. Five of 11 (45%) PF GGs and 6 of 9 (67%) ST GGs expressed the BRAF V600E mutation. No unique imaging features were identified in BRAF V600E mutation positive tumors. The majority of ST GGs were treated with surgery alone, whereas the majority of PF GGs required multimodality therapy. PF GGs had worse progression-free survival and a higher mortality rate compared with ST GGs. Unlike ST GGs, PF GGs are expansile, infiltrative, show dorsal predominant "paintbrush" enhancement, are not amenable to gross total resection, and have worse progression-free survival and mortality.

Diffusion tensor imaging of the superior cerebellar peduncle identifies patients with posterior fossa syndrome.

INTRODUCTION: Posterior fossa tumors are the most common brain tumor of children. Aggressive resection correlates with long-term survival. A high incidence of posterior fossa syndrome (PFS), impairing the quality of life in many survivors, has been attributed to damage to bilateral dentate nucleus or to cerebellar output pathways. Using diffusion tensor imaging (DTI), we examined the involvement of the dentothalamic tracts, specifically the superior cerebellar peduncle (SCP), in patients with posterior fossa tumors and the association with PFS. METHODS: DTI studies were performed postoperatively in patients with midline (n = 12), lateral cerebellar tumors (n = 4), and controls. The location and visibility of the SCP were determined. The postoperative course was recorded, especially with regard to PFS, cranial nerve deficits, and oculomotor function. RESULTS: The SCP travels immediately adjacent to the lateral wall of the fourth ventricle and just medial to the middle cerebellar peduncle. Patients with midline tumors that still had observable SCP did not develop posterior fossa syndrome (N = 7). SCPs were absent, on either preoperative (N = 1, no postoperative study available) or postoperative studies (N = 4), in the five patients who developed PFS. Oculomotor deficits of tracking were observed in patients independent of PFS or SCP involvement. CONCLUSION: PFS can occur with bilateral injury to the outflow from dentate nuclei. In children with PFS, this may occur due to bilateral injury to the superior cerebellar peduncle. These tracts sit immediately adjacent to the wall of the ventricle and are highly vulnerable when an aggressive resection for these tumors is performed.

A prognostic gene expression signature in infratentorial ependymoma.

Patients with ependymoma exhibit a wide range of clinical outcomes that are currently unexplained by clinical or histological factors. Little is known regarding molecular biomarkers that could predict clinical behavior. Since recent data suggest that these tumors display biological characteristics according to their location (cerebral vs. infratentorial vs. spinal cord), rather than explore a broad spectrum of ependymoma, we focused on molecular alterations in ependymomas arising in the infratentorial compartment. Unsupervised clustering of available gene expression microarray data revealed two major subgroups of infratentorial ependymoma. Group 1 tumors over expressed genes that were associated with mesenchyme, Group 2 tumors showed no distinct gene ontologies. To assess the prognostic significance of these gene expression subgroups, real-time reverse transcriptase polymerase chain reaction assays were performed on genes defining the subgroups in a training set. This resulted in a 10-gene prognostic signature. Multivariate analysis showed that the 10-gene signature was an independent predictor of recurrence-free survival after adjusting for clinical factors. Evaluation of an external dataset describing subgroups of infratentorial ependymomas showed concordance of subgroup definition, including validation of the mesenchymal subclass. Importantly, the 10-gene signature was validated as a predictor of recurrence-free survival in this dataset. Taken together, the results indicate a link between clinical outcome and biologically identified subsets of infratentorial ependymoma and offer the potential for prognostic testing to estimate clinical aggressiveness in these tumors.

Dermoid cyst of the posterior fossa.

Intracranial dermoid tumors represent a rare clinical entity accounting for 0.1-0.7% of all intracranial tumors. Their location in the posterior fossa is uncommon. We report a 16-year-old male patient who presented with clinical signs of increased intracranial pressure and cerebellar symptoms. The CT scan revealed a median cystic lesion of the fourth ventricle causing an active triventicular hydrocephalus. The MRI showed a median well shaped cystic lesion, of low signal intensity compared to the CSF, with capsular contrast enhancement. He underwent endoscopic third ventriculostomy before subtotal removal of the lesion. The postoperative course was uneventful, and the histological diagnosis was a dermoid cyst. Through this observation, we aim to discuss the clinical, and radiological aspects of the posterior fossa dermoid cyst, and to review the therapeutic strategies.

Pattern recognition methods in (1)H MRS monitoring in vivo of normal appearing cerebellar tissue after treatment of posterior fossa tumors.

The objective of this study was to investigate the metabolic responses of normal appearing cerebellar tissue after posterior fossa tumor treatment, and to identify characteristics of the particular treatment method. Moreover, this work examined the metabolic alterations of normal appearing tissue induced by a particular tumor state including resection, stagnation, progression, and recurrence. The studied group consisted of 29 patients treated for posterior fossa tumors. All of them were irradiated with a total dose of 54 Gy at 1.8 Gy/fraction (median values). In addition, 13 underwent chemotherapy, 25 underwent total tumor resection, 18 were tumor-free in control examinations, 5 had a stable disease, and tumor progression or recurrence was observed in 2 and 4 cases, respectively. The 69 spectra, acquired using a MRI/MRS 2T system, were analyzed using Partial Least Squares Discriminant Analysis (PLS-DA) with orthogonal signal correction (OSC) spectral filtering. A significantly elevated spectral region (0.97-1.55 ppm) was observed in patients after total resection in comparison to non-operated subjects. Patients treated with chemotherapy showed an elevated band between 1.15-1.75 and 2.7-3.0 ppm and had decreases in the remaining parts of the spectra. Increases in lactate and decreases in the remaining metabolites were characteristic for the tumor progression/recurrence group. Pattern recognition methods coupled with MRS revealed significant treatment-dependent alterations in normal appearing cerebellar tissue, as well as metabolic changes induced by tumor progression/recurrence.

Rhesus macaque as an animal model for posterior fossa syndrome following tumor resection.

BACKGROUND/AIMS: Posterior fossa tumors are the most common brain tumors in children. Surgeons usually remove these tumors via a midline incision through the posterior vermis of the cerebellum. Though often effective, this surgery causes hypotonia, ataxia, oculomotor deficits, transient mutism, difficulty in swallowing and nausea. To date, there is no animal model that mimics these complications. We found that the rhesus macaque is a good model for the consequences of this surgery. METHODS: We made a midline incision through the cerebellar vermis of one monkey to mimic the posterior fossa surgery. Then, we closely monitored the monkey for deficits following the surgery. RESULTS: In the first few days, the monkey exhibited nausea, hypotonia, ataxia, difficulty in swallowing and an absence of vocalization. At 28 days, we recorded eye movements and found severe deficits in the accuracy of rapid eye movements and smooth pursuit of a target. Additionally, the animal had trouble fixating and a rightward-beating nystagmus. Oculomotor signs persisted until we sacrificed the animal 99 days after surgery, but the other effects resolved by 37 days. CONCLUSION: Our surgery in a monkey caused the same postsurgical signs observed in humans. We expect to use this model to improve the posterior fossa surgery methods.

Postural balance in pediatric posterior fossa tumor survivors: Through impairments to rehabilitation possibilities.

BACKGROUND: The rehabilitation after pediatric brain tumors is a pressing issue in current neuro-oncology. The purpose of this study was to reveal the peculiarities of postural stability in pediatric posterior fossa tumor survivors as compared to the healthy controls. Additionally, we aimed to determine the feasibility of the balance biofeedback training for these patients. METHODS: We measured 6 postural stability parameters with the eyes opened and closed in 35 patients and 25 healthy controls aged 7-17. Further, the patients were divided into two groups: the intervention and waitlist. The intervention group was the first to undergo a 2-week biofeedback training designed to enhance balance control, while the waitlist group performed only the usual exercises. Then the groups were interchanged. Pre- and post-stability scores were measured in each condition. FINDINGS: The current results suggest the pronounced deficiency of stability in the patients. Their results in both opened and closed eyes conditions were similar. The post-training measurements revealed that some stability parameters were improved: ellipse square and mean root square oscillations in the frontal and sagittal planes. INTERPRETATION: The patients predictably demonstrated the significantly worse stability measurements as compared to the healthy controls. Moreover, they were shown not to use visual information to correct postural balance thus prompting us to assume severe deficits of the eye movements control due to the cerebellar pathology. This specificity, as well as the post-training significant improvement, emphasizes the clinical necessity to consider them when designing the rehabilitation protocols for posterior fossa tumor survivors.

Infratentorial Multinodular and Vacuolating Neuronal Tumor or Multinodular and Vacuolating Posterior Fossa Lesions of Unknown Significance? Clinico-Radiologic Findings from 2 Cases.

BACKGROUND: Infratentorial multinodular lesions resembling multinodular and vacuolating neuronal tumor of the cerebrum (MVNT) have been indicated in literature with 2 different names reflecting alternative perspectives: multinodular and vacuolating posterior fossa lesions of unknown significance (MV-PLUS), suggesting that these lesions may belong to a new entity, and MVNT of the brain, assuming that they actually correspond to infratentorial MVNT. Because of the limited number of cases reported and the absence of histopathologic data, it is unclear which denomination should be used. CASES DESCRIPTION: Two patients, a 41-year-old man (case 1) suffering headache and a 44-year-old man (case 2) with vertigo, underwent magnetic resonance imaging (MRI) examination. MRI showed, in both cases, multinodular lesions involving the vermis, broadly extending to the superior part of the right cerebellar hemisphere in case 1, and involving the superior paravermian part of the left cerebellar hemisphere in case 2. The follow-up period was 3 years in case 1 and 14 years in case 2. CONCLUSIONS: Infratentorial lesions show nodules with cystic or cyst-like signal intensity on MRI, a feature infrequently reported in supratentorial MVNT, and may involve the cortex. No variations were noted during a prolonged follow-up supporting the benign behavior of these lesions.

The effects of treatment for posterior fossa brain tumors on selective attention.

We sought to identify whether deficits in selective attention are present in pediatric brain tumor patients. Selective attention was assessed with covert-orienting, filtering, and visual-search tasks in 54 patients with either (1) posterior fossa (PF) tumors treated with cranial radiation and surgery (n = 22); (2) PF tumors treated with surgery alone (n = 17); or (3) non-CNS tumors (n = 15), who served as a patient control group. To account for normal development, patient performance was also compared with that of healthy age-matched controls (n = 10). We found that in PF tumor patients selective attention was impaired, regardless of whether they were treated with cranial radiation and surgery or surgery alone. However, patients treated with cranial radiation were most impaired. These patients may have greater damage to posterior brain regions know to mediate selective attention as the result of tumor location, effects of surgery, and higher doses of radiation to the posterior regions of the brain. These findings help to elucidate the potential impact of pediatric brain tumors and their treatment on discrete attentional skills.

[Intraoperative monitoring and its practical value in operations for tumors of the posterior cranial fossa in children].

The work is based on an analysis of the course of anesthetic aid, operative and early postoperative period in 62 patients aged from 15 months to 18 years with tumors of the posterior cranial fossa. The analysis concerned changes to the indices of systemic hemodynamics, findings of electrophysiological monitoring (electroencephalogram, acoustic stem induced potentials) and their interrelation with the outcomes of surgery. It was found that permanent disturbance of the heart rate such as bradycardia and tachycardia as well as the decreased indices of latency of peaks of the acoustic stem induced potentials and inter-peak intervals registered at the stage of removal of tumors of the posterior cranial fossa must be taken into consideration in the estimation of indications to medicinal narcosis in the postoperative period.

Role of the cerebellum in the neurocognitive sequelae of treatment of tumours of the posterior fossa: an update.

The lengthened survival of patients with tumours of the posterior fossa has brought awareness of the neurocognitive deficits present in this patient population. In the past, these deficits were thought to be caused by radiotherapy damaging supratentorial structures known to be responsible for cognitive processing. This notion led to the development of new treatment protocols to restrict damage to supratentorial regions by decreasing the radiation dose and the irradiated volume. However, these treatment protocols have only resulted in marginal improvements, sometimes at the expense of long-term survival. Moreover, the current published work reports that non-irradiated patients with tumours of the posterior fossa exhibit similar cognitive impairments to irradiated patients. The growth and treatment of tumours of the posterior fossa also damage infratentorial structures, including the cerebellum. Findings from anatomical, clinical, and neuroimaging studies support a role for the cerebellum in cognitive functions similar to those impaired in patients with a tumour of the posterior fossa. Despite these findings, research focused on the treatment of these patients and on decreasing their cognitive impairments either ignores that the cerebellum has been implicated in non-motor functions or argues against the possibility that damage to the cerebellum might result in cognitive sequelae. Future studies need to address the possibility that the cognitive impairments of patients with tumours of the posterior fossa might be determined by a combination of factors, including damage to the cerebellum. Recognition of the important cognitive contributions of the cerebellum might lead to improved cognitive outcome and quality of life for this patient population.

Facial emotion recognition in children treated for posterior fossa tumours and typically developing children: A divergence of predictors.

Facial emotion recognition (FER) deficits are evident and pervasive across neurodevelopmental, psychiatric, and acquired brain disorders in children, including children treated for brain tumours. Such deficits are thought to perpetuate challenges with social relationships and decrease quality of life. The present study combined eye-tracking, neuroimaging and cognitive assessments to evaluate if visual attention, brain structure, and general cognitive function contribute to FER in children treated for posterior fossa (PF) tumours (patients: n = 36) and typically developing children (controls: n = 18). To assess FER, all participants completed the Diagnostic Analysis of Nonverbal Accuracy (DANVA2), a computerized task that measures FER using photographs, while their eye-movements were recorded. Patients made more FER errors than controls (p < .01). Although we detected subtle deficits in visual attention and general cognitive function in patients, we found no associations with FER. Compared to controls, patients had evidence of white matter (WM) damage, (i.e., lower fractional anisotropy [FA] and higher radial diffusivity [RD]), in multiple regions throughout the brain (all p < .05), but not in specific WM tracts associated with FER. Despite the distributed WM differences between groups, WM predicted FER in controls only. In patients, factors associated with their disease and treatment predicted FER. Our study provides insight into predictors of FER that may be unique to children treated for PF tumours, and highlights a divergence in associations between brain structure and behavioural outcomes in clinical and typically developing populations; a concept that may be broadly applicable to other neurodevelopmental and clinical populations that experience FER deficits.

The relationship between intracranial pressure and the degree of brain swelling in patients subjected to infratentorial surgery.

BACKGROUND: In patients with supratentorial tumours, intracranial pressure is a strong predictor of intra-operative brain swelling and thresholds for ICP associated with brain swelling have been defined. Whether these ICP thresholds can be applied during infratentorial surgery is uncertain. We studied the relationship between subdural ICP and the degree of brain swelling after opening of the dura mater in patients subjected to infratentorial surgery. Thresholds for ICP associated with brain swelling were defined. METHODS: One hundred and nine adult patients subjected to infratentorial surgery were studied. Subdural ICP was measured immediately before opening of the dura and the degree of brain swelling was estimated by the neurosurgeon according to a four-point scale. FINDINGS: At ICP less than 7 mmHg brain swelling did not occur. In the range from 7 to 13 mmHg 21 of 39 patients (54%) had moderate swelling, but not pronounced swelling. At ICP greater than 13 mmHg some degree of swelling occurred in all patients, and at ICP exceeding 24 mmHg pronounced cerebral swelling was found in all patients. Using logistic regression analysis specific thresholds for ICP associated with brain swelling were defined as follows: at an ICP equal to or greater than 13 mmHg, brain swelling occurred with 95% probability; and at an ICP less than 6 mmHg brain swelling occurred with 5% probability. CONCLUSIONS: Subdural ICP measured before opening of the dura mater can predict the risk of brain swelling during infratentorial surgery. Thresholds for ICP associated with brain swelling are close to thresholds defined in patients undergoing supratentorial surgery.