Pediatric Posterior Fossa Tumor Survivors Research Articles

Effects of cognitive-motor intervention for pediatric posterior fossa tumor survivors: results of a pilot study.

The purpose of this prospective pilot study was to evaluate the feasibility and effects of cognitive-motor intervention on the cognitive and motor abilities of pediatric survivors of posterior fossa tumors. The study involved patients aged 7 to 18 years with cognitive deficits who had completed primary treatment for posterior fossa tumors. 25 participants (Mage=11.3 ± 2.93, 64% male; 17 medulloblastoma, 1 ependymoma, 1 desmoplastic medulloblastoma, 6 piloid astrocytoma; 22 in remission (Mmonths =45), 3 in stabilization (Mmonths=49)) were recruited from the Research Institute for Brain Development and Peak Performance. The intervention consisted of two phases with a 3-month break for home training, and a total duration of 6 months. Each phase lasted 7 weeks and included two assessment procedures (pre- and post-intervention) and 10 training sessions over a period of 5 weeks (two 3-hour sessions per week). At baseline and pre- and post-intervention, all participants underwent a battery of cognitive and motor tests. Each training session included gross motor training (GMT), graphomotor training (GT), and cognitive-motor training (CMT). Statistical analysis was performed using the Friedman test for repeated measures and post-hoc Durbin-Conover test. The results indicated significant improvements in visuospatial working memory, visual attention, eye-hand coordination, semantic verbal fluency, auditory-motor synchronization, reaction time, and a decrease in the rate of ataxia. These improvements remained stable even in the absence of direct intervention. The findings demonstrate positive effects and feasibility of the intervention and suggest the need for further research in this area including randomized controlled feasibility studies with a larger sample.

The Role of the Cerebellum in Visual-Spatial Memory in Pediatric Posterior Fossa Tumor Survivors.

The cerebellum is involved in motor and non-motor functions. Cerebellar lesions can underlie the disruption of various executive functions. The violation of executive functions in cerebellar lesions is a serious problem, since children, after completing treatment, must return to school, finish their education, and get a profession. One of the important executive functions is working memory, which contributes to academic success. Deficits of verbal working memory in cerebellar tumors have been studied, in contrast to visual-spatial working memory. To assess this issue, 101 patients who survived cerebellar tumors and 100 healthy control subjects performed a visual-spatial working memory test. As a result, in children who survived cerebellar tumors, visual-spatial working memory is impaired compared to the control group. Moreover, with age, and hence the time since the end of treatment, the number of elements that children can retain in visual-spatial working memory increases, but still remains smaller compared to the control group. Our findings complement the idea of cerebellar involvement in visual-spatial working memory and suggest that it is disrupted by cerebellar lesions in children.

Executive and social functioning in pediatric posterior fossa tumor survivors and healthy controls.

Executive and social functioning difficulty is well established in pediatric brain tumor survivors. Few studies have compared posterior fossa (PF) tumor survivors in comparison to their peers. The relationship between attention, processing speed, working memory, fatigue, and executive and social functioning was investigated to better understand the factors that impact executive and social functioning in PF tumor populations. Sixteen medulloblastomas, 9 low-grade astrocytomas (LGAs), and 17 healthy controls recruited from 4 sites completed measures of working memory and processing speed, and self-reported fatigue. One parent completed questionnaires on executive and social functioning. There were no significant differences among all 3 groups on parent-reported executive and social functioning; of note, parents of LGA survivors expressed greater concerns regarding behavioral and cognitive regulation than did parents of medulloblastoma survivors and healthy controls. Parent-reported attention was related to parent-reported emotion, behavior, and cognitive regulation. Worse self-reported fatigue was associated with greater emotional dysregulation for the 2 PF tumor groups. Parents of PF tumor survivors described their children as performing similarly to their peers in most facets of executive and social functioning. While LGA survivors are traditionally thought to have more favorable outcomes, our finding of parent-reported executive functioning concerns to be worse for this group highlights the importance of long-term follow-up for all PF tumor survivors. Additionally, significant effects of attention on aspects of executive functioning in PF tumor survivors may inform current clinical practice and the future development of more effective interventions.

Comparison of neuropsychological functioning in pediatric posterior fossa tumor survivors: Medulloblastoma, low-grade astrocytoma, and healthy controls.

Neuropsychological comparison of medulloblastoma (MB) and cerebellar low-grade astrocytoma (LGA) survivors to controls can clarify treatment-related neurocognitive late effects. While both brain tumor groups undergo surgery to the posterior fossa, children with MB additionally receive craniospinal irradiation with boost and chemotherapy. This study provides an updated comparison of neuropsychological functioning in these two groups and examines effects of demographic risk factors upon outcomes. Forty-two children (16 MB, nine LGA, and 17 controls) completed measures of intellectual functioning, verbal learning/memory, visual-motor integration, and fine-motor functioning. The effects of age at diagnosis, time since diagnosis, gender, fatigue, and social status on neuropsychological functioning were examined. MB survivors demonstrated the worst neurocognitive late effects, but they were less severe and extensive than in prior studies. LGA survivors' mean scores were below normative expectations in working memory, processing speed, and fine-motor functioning. In this overall sample, processing speed difficulties were independent of fine-motor functioning and fatigue. Higher parental education was associated with better intellectual functioning, working memory, delayed recall, and visual-motor integration. Neuropsychological function was not associated with gender, age at diagnosis, or time since diagnosis. The results support that contemporary treatment approaches with craniospinal irradiation plus boost and chemotherapy confer the greatest risk for late effects, while surgical resection is associated with subtle but important neurocognitive difficulties. Ultimately, this study furthers our understanding of factors impacting neuropsychological function in pediatric MB and LGA survivors and contributes to empirical support for close monitoring and targeted interventions into survivorship.

The feasibility and efficacy of short-term visual-motor training in pediatric posterior fossa tumor survivors.

Pediatric posterior fossa tumor (PFT) survivors experience a range of cognitive and motor impairments that require timely rehabilitation of these functions. In Russia, rehabilitation services are only just beginning to be formed; therefore, it is necessary to test rehabilitation protocols for children surviving cancer. To evaluate the efficacy of short-term cognitive and motor training (CMT) aimed on visual-motor integration in PFT survivors using training devices. "Single center" quasi randomized controlled experiment. Outpatients of the Russkoe Pole Rehabilitation Center. The 63 children cancer survivors between the ages of 6 and 17 years. The baseline level of cognitive and motor functions was assessed in all participants. Then the sample of patients split into two subgroups of equal sex, age, and diagnosis. The intervention subgroup received six sessions of CMT for two weeks, and the other subgroup underwent 'empty' two weeks with no intervention. Reassessment of motor and cognitive functions was conducted in all participants. Then the subgroups changed: the first subgroup underwent 'empty' two weeks, and the second subgroup completed the CMT, and further reassessment was provided. The primary results demonstrate an increase in gross and fine motor skills, motor coordination, visual-motor integration, and visual processing after CMT. Secondary results show that the age at onset is an important factor in the subsequent decline in cognitive, motor functions, and eye movements. Children with medulloblastoma perform worse on motor tests than children with astrocytoma. A tumor in the IV ventricle is the most harmful, and a tumor in the cerebellar hemispheres is the least harmful to a child's cognitive and motor development. This study shows the effectiveness of a short-term CMT program for children who survived PFT. The study also found that cognitive, motor, and visual-motor functions are affected by the tumor's localization, malignancy, and the child's age at onset. Short-term rehabilitation methods can be useful in pediatric oncological practice. Reconstruction of cognitive functions can occur during the training of more "simple" functions, such as hand-eye integration. The study makes a significant contribution to the methods of short-term rehabilitation in children who survived cancer.

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

BackgroundThe 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. MethodsWe 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. FindingsThe 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. InterpretationThe 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.

Cognitive and Motor Training in Pediatric Posterior Fossa Tumor Survivors

Cognitive and Motor Training in Pediatric Posterior Fossa Tumor Survivors

Relationships between Regional Radiation Doses and Cognitive Decline in Children Treated with Cranio-Spinal Irradiation for Posterior Fossa Tumors.

Pediatric posterior fossa tumor (PFT) survivors who have been treated with cranial radiation therapy often suffer from cognitive impairments that might relate to IQ decline. Radiotherapy (RT) distinctly affects brain regions involved in different cognitive functions. However, the relative contribution of regional irradiation to the different cognitive impairments still remains unclear. We investigated the relationships between the changes in different cognitive scores and radiation dose distribution in 30 children treated for a PFT. Our exploratory analysis was based on a principal component analysis (PCA) and an ordinary least square regression approach. The use of a PCA was an innovative way to cluster correlated irradiated regions due to similar radiation therapy protocols across patients. Our results suggest an association between working memory decline and a high dose (equivalent uniform dose, EUD) delivered to the orbitofrontal regions, whereas the decline of processing speed seemed more related to EUD in the temporal lobes and posterior fossa. To identify regional effects of RT on cognitive functions may help to propose a rehabilitation program adapted to the risk of cognitive impairment.

DTI fiber tractography of cerebro-cerebellar pathways and clinical evaluation of ataxia in childhood posterior fossa tumor survivors.

Pediatric posterior fossa (PF) tumor survivors experience long-term motor deficits. Specific cerebrocerebellar connections may be involved in incidence and severity of motor dysfunction. We examined the relationship between long-term ataxia as well as fine motor function and alteration of differential cerebellar efferent and afferent pathways using diffusion tensor imaging (DTI) and tractography. DTI-based tractography was performed in 19 patients (10 pilocytic astrocytoma (PA) and 9 medulloblastoma patients (MB)) and 20 healthy peers. Efferent Cerebello-Thalamo-Cerebral (CTC) and afferent Cerebro-Ponto-Cerebellar (CPC) tracts were reconstructed and analyzed concerning fractional anisotropy (FA) and volumetric measurements. Clinical outcome was assessed with the International Cooperative Ataxia Rating Scale (ICARS). Kinematic parameters of fine motor function (speed, automation, variability, and pressure) were obtained by employing a digitizing graphic tablet. ICARS scores were significantly higher in MB patients than in PA patients. Poorer ICARS scores and impaired fine motor function correlated significantly with volume loss of CTC pathway in MB patients, but not in PA patients. Patients with pediatric post-operative cerebellar mutism syndrome showed higher loss of CTC pathway volume and were more atactic. CPC pathway volume was significantly reduced in PA patients, but not in MB patients. Neither relationship was observed between the CPC pathway and ICARS or fine motor function. There was no group difference of FA values between the patients and healthy peers. Reduced CTC pathway volumes in our cohorts were associated with severity of long-term ataxia and impaired fine motor function in survivors of MBs. We suggest that the CTC pathway seems to play a role in extent of ataxia and fine motor dysfunction after childhood cerebellar tumor treatment. DTI may be a useful tool to identify relevant structures of the CTC pathway and possibly avoid surgically induced long-term neurological sequelae.

Executive function deficits in pediatric cerebellar tumor survivors.

Besides motor function the cerebellum subserves frontal lobe functions. Thus, we investigated executive functions in pediatric posterior fossa tumor survivors. We tested information processing, aspects of attention, planning and intelligence in 42 pediatric posterior fossa tumor survivors (mean age 14.63yrs, 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. 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. 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.

Cerebral white matter fractional anisotropy and tract volume as measured by MR imaging are associated with impaired cognitive and motor function in pediatric posterior fossa tumor survivors.

Disease and therapy cause brain damage and subsequent functional loss in pediatric patients with posterior fossa tumors. Treatment-related toxicity factors are resection in patients with pilocytic astrocytoma (PA) and, additionally, cranio-spinal irradiation together with chemotherapy in patients with medulloblastoma (MB). We tested whether damage to white matter (WM) as revealed by diffusion tensor MR imaging (DTI) correlated with specific cognitive and motor impairments in survivors of pediatric posterior fossa tumors. Eighteen MB (mean age ± SD, 15.2 ± 4.9 y) and 14 PA (12.6 ± 5.0 y) survivors were investigated with DTI on a 3-Tesla-MR system. We identified fractional anisotropy (FA) of WM, the volume ratio of WM to gray matter and cerebrospinal fluid (WM/GM + CSF), and volume of specific frontocerebellar tracts. Ataxia was assessed using the International Cooperative Ataxia Rating Scale (ICARS), while the Wechsler Intelligence Scale for Children determined full-scale intelligence quotients (FSIQ). Amsterdam Neuropsychological Tasks (ANT) was used to assess processing speed. Handwriting automation was analyzed using a digitizing graphic tablet. The WM/GM + CSF ratio correlated significantly with cognitive measures (IQ, P = 0.002; ANT baseline speed, P = 0.04; ANT shifting attention, P = 0.004). FA of skeletonized tracts correlated significantly with FSIQ (P = 0.008), ANT baseline speed (P = 0.028) and ANT shifting attention (P = 0.045). Moreover, frontocerebellar tract volumes correlated with both the FSIQ (P = 0.011) and ICARS (P = 0.007). DTI provides a method for quantification of WM damage by tumor and by therapy-associated effects in survivors of pediatric posterior fossa tumors. DTI-derived WM integrity may be a representative marker for cognitive and motor deterioration.

Morphological brain lesions of pediatric cerebellar tumor survivors correlate with inferior neurocognitive function but do not affect health-related quality of life.

We aimed to determine whether extent of morphological brain injury in pediatric cerebellar tumor survivors correlates with neurocognitive function and health-related quality of life (HrQoL). Seventeen cerebellar pilocytic astrocytoma (cPA) and 17 medulloblastoma (MB) survivors were examined for HrQoL, intelligence using the German version of the WISC-III, attention, working memory, and visual motor coordination. MRI scans were analyzed for extent of posterior fossa brain tissue loss. We found significant correlations between amount and extent morphological brain lesions of pediatric cerebellar tumor survivors and several cognitive impairments including intelligence and attention in both patient groups. These were in total more pronounced in MB patients when compared to cPA patients. Still, function loss and brain lesions detected on conventional MRI did not influence HrQoL. These findings support the notion that long-term neurocognitive deficits of pediatric posterior fossa tumor survivors significantly correlate with brain tissue damage. The cerebellum plays a role in regulating higher-order functions. On the contrary, the extent brain injury is not detected by HrQoL assessment.

Frontocerebellar tract lesions revealed by tractography in pediatric posterior fossa tumor survivors

Frontocerebellar tract lesions revealed by tractography in pediatric posterior fossa tumor survivors

An fMRI investigation of working memory and its relationship with cardiorespiratory fitness in pediatric posterior fossa tumor survivors who received cranial radiation therapy

The present study investigated the relationship between cardiorespiratory fitness and executive functioning in pediatric brain tumor survivors who received cranial radiation. This population is known to show executive dysfunction and lower rates of aerobic exercise compared to peers. Nine adolescent survivors of pediatric posterior fossa tumor completed an n-back working memory task during a functional MRI scan, as well as cardiorespiratory fitness testing on a cycle ergometer. Neuroimaging findings indicated typical activation patterns associated with working memory, mainly in the frontal-parietal network. Higher cardiorespiratory fitness was related to better performance on a behavioral measure of working memory and more efficient neural functioning. This study provides preliminary evidence that cardiorespiratory fitness may be related to executive functioning, particularly working memory, in pediatric brain tumor survivors. Descriptions of the brain regions recruited for working memory by pediatric brain tumor survivors may be used to inform future interventions or indicators of treatment efficacy.

Cardiorespiratory Fitness in Survivors of Pediatric Posterior Fossa Tumor

Advances in medical therapies have greatly improved survivorship rates in children diagnosed with brain tumor; as a result, morbidities associated with survivorship have become increasingly important to identify and address. In general, pediatric posterior fossa tumor survivors tend to be less physically active than peers. This may be related to late effects of diagnosis and treatment, including cardiovascular, endocrine, psychological, and neurocognitive difficulties. Exercise has been shown to be effective in improving physical functioning, mood, and even cognitive functioning. Consequently, the benefits of physical exercise need to be explored and incorporated into the daily lives of pediatric posterior fossa tumor survivors. The primary aim of the present study was to establish the feasibility and safety of cardiorespiratory fitness testing in pediatric posterior fossa tumor survivors who had received cranial radiation therapy. In addition, comparing our cohort with previously published data, we found that pediatric posterior fossa tumor survivors tended to be less fit than children with pulmonary disease and healthy controls and approximately as fit as children with chronic heart disease and survivors of other types of childhood cancer. The importance of cardiorespiratory fitness in pediatric posterior fossa tumor survivors is discussed along with implications for future directions.

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.

Supratentorial Neurometabolic Alterations in Pediatric Survivors of Posterior Fossa Tumors

Therapy and tumor-related effects such as hypoperfusion, internal hydrocephalus, chemotherapy, and irradiation lead to significant motor and cognitive sequelae in pediatric posterior fossa tumor survivors. A distinct proportion of those factors related to the resulting late effects is hitherto poorly understood. This study aimed at separating the effects of neurotoxic factors on central nervous system metabolism by using H-1 MR spectroscopy to quantify cerebral metabolite concentrations in these patients in comparison to those in age-matched healthy peers. Fifteen patients with World Health Organization (WHO) I pilocytic astrocytoma (PA) treated by resection only, 24 patients with WHO IV medulloblastoma (MB), who additionally received chemotherapy and craniospinal irradiation, and 43 healthy peers were investigated using single-volume H-1 MR spectroscopy of parietal white matter and gray matter. Concentrations of N-acetylaspartate (NAA) were significantly decreased in white matter (p < 0.0001) and gray matter (p < 0.0001) of MB patients and in gray matter (p = 0.005) of PA patients, compared to healthy peers. Decreased creatine concentrations in parietal gray matter correlated significantly with older age at diagnosis in both patient groups (MB patients, p = 0.009, r = 0.52; PA patients, p = 0.006, r = 0.7). Longer time periods since diagnosis were associated with lower NAA levels in white matter of PA patients (p = 0.008, r = 0.66). Differently decreased NAA concentrations were observed in both PA and MB groups of posterior fossa tumor patients. We conclude that this reflects a disturbance of the neurometabolic steady state of normal-appearing brain tissue due to the tumor itself and to the impact of surgery in both patient groups. Further incremental decreases of metabolite concentrations in MB patients may point to additional harm caused by irradiation and chemotherapy. The stronger decrease of NAA in MB patients may correspond to the additional damage of combined irradiation and chemotherapy on neuroaxonal cell viability and number.

Impairment of executive functions in pediatric posterior fossa tumor survivors

Purpose: Apart from controlling motor function the cerebellum modulates higher cognitive and emotional functions. We investigated executive functions in pediatric posterior fossa tumor survivors.

Loss of fine motor function correlates with ataxia and decline of cognition in cerebellar tumor survivors

Motor and cognitive function losses resemble handicaps in pediatric posterior fossa tumor survivors. Several factors determine type and extent of impairment. We quantified loss of fine motor function and its association with ataxia and intelligence in patients with and without adjuvant treatment. Fine motor function, extent of ataxia and cognitive function were assessed in 25 medulloblastoma (MB) and 16 cerebellar pilocytic astrocytoma (PA) patients at least 1 year after completion of therapy. Kinematic parameters (speed, automation, variability, and pressure) of different movement complexity levels were investigated employing a digitizing graphic tablet. Degree of ataxia was quantified using the International Cooperative Ataxia Rating Scale and cognition was determined using the Wechsler Intelligence Scale. Kinematic parameters of low and high complexity tasks as well as ataxia of MB patients were strongly impaired. Fine motor impairment was weaker in PA patients, but still evident in the complex task of writing. Ataxia was significantly more pronounced in medulloblastoma patients. Young age and short recovery time correlated significantly with impaired kinematic parameters. Ataxia was strongly associated with inferior fine motor function. Cognition, especially performance IQ, was associated with dysfunctional kinematic parameters. The digitizing tablet detected extent of fine motor function loss at varying levels of complexity of pediatric cerebellar tumor survivors. This tool promises to be a potentially effective method for measuring fine motor function in clinical trials and may be helpful in studying mechanisms of neurotoxicity in posterior fossa tumor patients as well as success of rehabilitation.

Evaluation of diadochokinesis and handwriting movements of pediatric posterior fossa tumor survivors

Evaluation of diadochokinesis and handwriting movements of pediatric posterior fossa tumor survivors