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.

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.

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.

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.

Visual and ocular motor outcomes in children with posterior fossa tumors.

PURPOSE: To describe the clinical characteristics and visual and ocular motor outcomes of a large cohort of pediatric patients treated for tumors of the posterior cranial fossa. METHODS: The medical records of all patients with posterior fossa tumors evaluated by the ophthalmology services at two large tertiary care academic hospitals between 2005 and 2011 were reviewed retrospectively. Data abstracted for each study patient included demographic information, presenting signs and symptoms, pathologic diagnosis, and results of the most recent ophthalmology examination. RESULTS: A total of 139 patients were included. Visual outcomes were categorized as "good" (bilateral acuity of 20/20-20/40) in 101 patients (72.7%), "fair" (<20/40-20/200 in one or both eyes) in 12 patients (8.6%), or "poor" (<20/200 in one or both eyes) in 9 patients (6.5%). Patients with medulloblastoma and ependymoma had a significantly greater risk of a poor or fair visual outcome than those with juvenile pilocytic astrocytoma (both P < 0.05), independent of age and sex. Thirty-two patients (23.0%) developed nystagmus, and 59 patients (42.4%) developed strabismus. Twenty-four patients (17.3%) underwent eye muscle surgery for persistent strabismus. CONCLUSIONS: The majority of patients had good visual outcomes, although ocular motor abnormalities were common. Tumor type was a significant risk factor for permanent vision loss.

A Review of Visual and Oculomotor Outcomes in Children With Posterior Fossa Tumors.

Tumors of the posterior fossa represent the most common solid malignancy of childhood and can affect the visual system in several ways. This article outlines the relevant visual anatomy affected by these tumors and reviews the visual and oculomotor outcomes associated with the following 3 most common tumor types-medulloblastoma, juvenile pilocytic astrocytoma, and ependymoma. The available data suggest that the rate of permanent vision loss is low (5.9%-8.3%), with patients having juvenile pilocytic astrocytoma demonstrating the best outcomes. The rate of long-term strabismus (25%-29.1%) and nystagmus (12.5%-18%) is higher and associated with significant morbidity.

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.

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?

Intraoperative neurophysiological monitoring during resection of infratentorial lesions: the surgeon's view.

OBJECTIVE Methods of choice for neurophysiological intraoperative monitoring (IOM) within the infratentorial compartment mostly include early brainstem auditory evoked potentials, free-running electromyography, and direct cranial nerve (CN) stimulation. Long-tract monitoring with somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) is rarely used. This study investigated the incidence of IOM alterations during posterior fossa surgery stratified for lesion location. METHODS Standardized CN and SEP/MEP IOM was performed in 305 patients being treated for various posterior fossa pathologies. The IOM data were correlated with lesion locations and histopathological types as well as other possible confounding factors. RESULTS Alterations in IOM were observed in 158 of 305 cases (51.8%) (CN IOM alterations in 130 of 305 [42.6%], SEP/MEP IOM alterations in 43 of 305 [14.0%]). In 15 cases (4.9%), simultaneous changes in long tracts and CNs were observed. The IOM alterations were followed by neurological sequelae in 98 of 305 cases (32.1%); 62% of IOM alterations resulted in neurological deficits. Sensitivity and specificity for detection of CN deficits were 98% and 77%, respectively, and 95% and 85%, respectively, for long-tract deficits. Regarding location, brainstem and petroclival lesions were closely associated with concurrent CN IOM and SEP/MEP alterations. CONCLUSIONS The incidence of IOM alterations during surgery in the posterior fossa varied widely between different lesion locations and histopathological types. This analysis provides crucial information on the necessity of IOM in different surgical settings. Because MEP/SEP and CN IOM alterations were commonly observed during posterior fossa surgery, the authors recommend the simultaneous use of both modalities based on lesion location.

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.

Multifocal Supra and Infratentorial Medulloblastoma in an Adult: Histologic, Immunohistochemical, and Molecular Evaluation of a Rare Case and Review of the Literature.

Multifocal medulloblastomas (MMBs) in adults are exceedingly rare with only 5 reported cases to date. Medulloblastoma in adult differ from its childhood counterpart by being more often lateral in location, desmoplastic in morphology, and better in clinical prognosis. Little is known, however, about the characteristic features of MMB. This is particularly true for their molecular profiles. To date, molecular characteristics of multifocal medulloblastoma have been reported only once. Here, we present the second case of multifocal medulloblastoma along with its detailed morphology, imaging features, and molecular profiles with a critical review of the literature. We believe that MMB should be reported in detail to better understand their behavior, characterize their molecular profiles, and establish therapeutic protocols.

Executive function deficits in pediatric cerebellar tumor survivors.

BACKGROUND AND AIMS: Besides motor function the cerebellum subserves frontal lobe functions. Thus, we investigated executive functions in pediatric posterior fossa tumor survivors. METHODS: We tested information processing, aspects of attention, planning and intelligence in 42 pediatric posterior fossa tumor survivors (mean age 14.63 yrs, SD 5.03). Seventeen low-grade tumor patients (LGCT) were treated with surgery only and 25 high-grade tumors patients (HGCT) received postsurgical adjuvant treatment. We evaluated simple reaction time, executive functioning, i.e. visuospatial memory, inhibition, and mental flexibility using the Amsterdam Neuropsychological Tasks program, whereas forward thinking was assessed with the Tower of London-test. Intelligence was determined using the Wechsler Intelligence Scale. Ataxia was assessed with the International Cooperative Ataxia Rating Scale. RESULTS: About one third of each patient group showed forward thinking scores below one standard deviation of the norm. Impaired forward thinking correlated significantly with degree of ataxia (r = -0.39, p = 0.03) but not with fluid intelligence. Both patient groups exhibited executive function deficits in accuracy and reaction speed in more difficult tasks involving information speed and attention flexibility. Still, HGCT patients were significantly slower and committed more errors. Working memory was inferior in HGCT patients. CONCLUSION: Pediatric cerebellar tumor survivors with different disease and treatment related brain damage exhibit similar patterns of impairment in executive functioning, concerning forward thinking, inhibition and mental flexibility. The deficits are larger in high-grade tumor patients. The pattern of function loss seen in both groups is most probably due to comparable lesions to cerebro-cerebellar circuits that are known to modulate critical executive functions.

[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.

Physical functioning in pediatric survivors of childhood posterior fossa brain tumors.

BACKGROUND: Survival rates for children diagnosed with posterior fossa brain tumors (PFBTs) have improved significantly over the past several decades, and long-term functioning assessments have become priorities. These evaluations have occurred frequently in adults but only rarely in children. This study describes a cross-sectional assessment of physical functioning in pediatric survivors of PFBTs using the Bruininks-Osteretsky Test of Motor Performance, Second Edition (BOT-2). METHODS: Primary analyses compared BOT-2 scores to normative data using 1-sample t tests for each gross motor subscale (Bilateral Coordination, Balance, Running Speed/Agility, Strength) and motor-area composite (Body Coordination and Strength and Agility). Second, the cohort was stratified by diagnostic or treatment variables. Group differences and groups vs norms were evaluated using independent 2-sample and 1-sample t tests, respectively. Primary analyses compared BOT-2 scores with normative data using 1-sample t tests for each gross motor subscale (Bilateral Coordinationcoordination, Balance, Running Speed/Agility, Strength) and motor-area composite (Body Coordination and Strength and Agility). Second, the cohort was stratified by diagnostic or treatment variables. Group differences and groups vs norms were evaluated using independent 2-sample and 1-sample t tests, respectively. RESULTS: Mean age of 30 participants was 11.4 years (range, 4.9y-18.2y), and mean time from diagnosis was 6.1 years (range, 1.1y-16.7y). Cerebellar astrocytoma (43.3%) and medulloblastoma (40%) were the most common diagnoses. As a group, significantly decreased functioning, compared with norms, was observed in Balance (P < .001) and Running Speed/Agility (P = .005). Specifically in Balance, 21 (70%) participants performed below or well-below average. Participants with a non-astrocytoma performed significantly lower than norms in all areas, independent of age at diagnosis. Survivors with tumors infiltrating the vermis demonstrated significantly lower Body Coordination than norms (P < .001). CONCLUSIONS: Pediatric survivors of PFBTs demonstrated decreased physical functioning, most notably in Balance. These data underscore the need for further research and implementation of physical activity programs aimed specifically at approaches to minimize physical limitations.

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.

Posterior fossa tumors and their impact on sleep and ventilatory control: a clinical perspective.

The cerebellum, classically viewed as a motor structure of the brain, may play a role in respiration. Brainstem dysfunction has been implicated in sleep disordered breathing (SDB), but apnea after surgery of brain tumors in the posterior fossa, not involving the brainstem has been reported. We report four cases with posterior fossa tumors without brainstem invasion who suffered SDB after surgery diagnosed by polysomnography (PSG). Advanced MRI techniques with DTI were used to find correlations with SDB. Abnormal signals in the superior, middle and inferior cerebellar peduncles were seen in these patients with the most severe changes in the inferior peduncle. SDB may be under diagnosed in the setting of posterior fossa tumors without brainstem involvement. Damage to the cerebellar peduncles, especially the inferior cerebellar peduncle, without brainstem involvement, can cause significant disruption of respiration.

Executive dysfunction in pediatric posterior fossa tumor survivors: a systematic literature review of neurocognitive deficits and interventions.

Improved medical therapies have increased survivorship rates for children with posterior fossa tumors; resultantly, morbidities associated with survivorship, such as executive function deficits, have become increasingly important to identify and address. Executive dysfunction can impact academic achievement as well as functional outcomes. We summarize studies describing executive functioning deficits in pediatric posterior fossa tumor survivors who received cranial radiation therapy and intervention studies that have targeted executive functioning deficits. Previous theoretical models describing the etiology of these deficits are reviewed, and a new, more comprehensive model is proposed. Future research should move toward incorporating neuroimaging, longitudinal designs, and multiple informants.