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  • 1
    Language: English
    In: Child's Nervous System, 2011, Vol.27(11), pp.1895-1902
    Description: Byline: Lindy Musial-Bright (1), Louisa Panteli (1), Pablo Hernaiz Driever (1) Keywords: Low-grade glioma; Childhood cancer survivors; Quality of life; Disability Abstract: Purpose The purpose of this study was to determine pediatric low-grade glioma survivors' quality of life and late morbidity including motor, sensory, and cognitive deficits. Methods We surveyed 49 survivors and their parents (KINDL questionnaire). Results Despite tumor and treatment-associated morbidity, survivors (25 boys and 24 girls, median age at diagnosis 7.8 years), but not their parents, rated their total quality of life higher than their peers. Although all survivors had some late morbidity, half of them were able to conduct their daily lives without restriction. Conclusion These results reflect survivors' effective coping mechanisms and underscore the difficulties of assessing quality of life in pediatric populations. Author Affiliation: (1) Department of Pediatric Oncology and Hematology, Charite-Universitatsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany Article History: Registration Date: 16/04/2011 Received Date: 24/01/2011 Accepted Date: 15/04/2011 Online Date: 03/05/2011
    Keywords: Low-grade glioma ; Childhood cancer survivors ; Quality of life ; Disability
    ISSN: 0256-7040
    E-ISSN: 1433-0350
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  • 2
    Language: English
    In: Cancer Research, 04/15/2011, Vol.71(8 Supplement), pp.3452-3452
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
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  • 3
    Language: English
    In: Clinical laboratory, 2016, Vol.62(4), pp.667-77
    Description: The present study was aimed to prove the usefulness of a new diagnostic plot (Hema-Plot), illustrating the relationship between the hemoglobin content of reticulocytes (Ret-He) as a marker of functional iron deficiency and the difference between the reticulocyte and erythrocyte hemoglobin content (Delta-He) as a marker of an impaired hemoglobinization of newly formed reticulocytes occurring during inflammatory processes, to differentiate between various disease-specific types of anemia. A complete blood and reticulocyte count was performed on routine EDTA blood samples from 345 patients with and without various disease-specific types of anemia using the Sysmex XN-9000 hematology analyzer: blood healthy newborns (n = 23), blood healthy adults (n = 31), patients suffering from anemia of chronic disease (ACD) due to diverse oncological, chronic inflammatory, or autoimmune diseases (total n = 138) with (n = 65) and without therapy (n = 73), patients with thalassemia and/or hemoglobinopathy (n = 18), patients with iron deficiency anemia (IDA) (n = 35), patients with a combination of ACD and IDA (n = 17), as well as patients suffering from sepsis (total n = 83) with (n = 32) and without therapy (n = 51). The results for Ret-He, Delta-He, and C-reactive protein (CRP) were statistically compared (Mann-Whitney U Test) between the particular patient groups and the diagnostic plots were drawn. Delta-Hemoglobin showed a statistically significant difference between blood healthy newborns and blood healthy adults (p ≤ 0.05), while Ret-He and C-reactive protein did not. In addition, of all three biomarkers only Delta-He showed a statistically significant difference (p ≤ 0.05) between the ACD/IDA and IDA cohort. Delta-He, Ret-He, and CRP showed a statistically significant difference between patient cohorts with and without therapy suffering from ACD, ACD/IDA, and sepsis before and after medical therapy (p ≤ 0.05). The Hema-Plot illustrated the dynamic character of Ret-He and Delta-He, notably in inflammation-based types of anemia like ACD or ACD/ IDA. Delta-He is a new biomarker clearly distinguishing between inflammation-based types of anemia before and after medical therapy, as well as between ACD/IDA and IDA. The new Hema-Plot is a helpful tool for differential diagnosis and disease-monitoring in various types of disease-specific anemia, especially in ACD and ACD/IDA. The Hema-Plot can be used to identify non-adherent patients or an insufficient therapy.
    Keywords: Anemia -- Diagnosis ; Erythrocytes -- Chemistry ; Hemoglobins -- Analysis ; Reticulocytes -- Chemistry
    ISSN: 1433-6510
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  • 4
    In: Pediatric Blood & Cancer, July 2015, Vol.62(7), pp.1252-1258
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1002/pbc.25485/abstract Byline: Stefan M. Rueckriegel, Harald Bruhn, Ulrich W. Thomale, Pablo Hernaiz Driever Background 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. Procedures Eighteen MB (mean age[+ or -]SD, 15.2[+ or -]4.9 y) and 14 PA (12.6[+ or -]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. Results 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). Conclusion 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. Pediatr Blood Cancer 2015;62:1252-1258. [c] 2015 Wiley Periodicals, Inc. Article Note: Conflicts of interest: Nothing to declare.
    Keywords: Diffusion Tensor Imaging ; Dti ; Pediatric Brain Tumors ; White Matter Integrity
    ISSN: 1545-5009
    E-ISSN: 1545-5017
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  • 5
    Language: English
    In: Child's Nervous System, April, 2013, Vol.29(4), p.597(11)
    Description: Byline: Verena Soelva (1), Pablo Hernaiz Driever (2), Alexander Abbushi (1), Stefan Rueckriegel (2), Harald Bruhn (3), Wilhelm Eisner (4), Ulrich-Wilhelm Thomale (1) Keywords: Diffusion tensor imaging; Tractography; Pediatric brain tumor; Posterior fossa surgery; Cerebellar mutism Abstract: Objective Fronto-cerebellar association fibers (FCF) are involved in neurocognitive regulatory circuitry. This may also be relevant for cerebellar mutism syndrome (CMS) as a complication following posterior fossa tumor removal in children. In the present study, we investigated FCF by diffusion tensor imaging in affected children and controls. Methods Diffusion-weighted MR imaging at 3 T (GE) allowed tractography of FCF using a fiber tracking algorithm software (Brainlab 2.6) in 29 patients after posterior fossa tumor removal and in 10 healthy peers. Fiber tract volumes were assessed and fiber signals were evaluated in a semiquantitative manner along the anatomical course. Results Volumes of FCF revealed significant diminished values in pediatric patients with symptoms of CMS (19.3+-11.7 cm.sup.3) when compared with patients without symptoms of CMS (26.9+-11.9 cm.sup.3) and with healthy peers (36.5+-13.82 cm.sup.3). In medulloblastoma patients, the volume of FCF was also significantly reduced in patients with symptoms of CMS despite having the same antitumor therapy. In semiquantitative analysis of the fiber tract signals, differences were observed in the superior cerebellar peduncles and midline cerebellar structures in patients with symptoms of CMS. Conclusion Using DTI, which allows the visualization of fronto-cerebellar fiber tracts, lower FCF tract volumes and diminished fiber signal intensities at the level of the superior cerebellar peduncles and in midline cerebellar structures were identified in patients with postoperative symptoms of CMS. Our study refers to the role of a neural circuitry between frontal lobes and the cerebellum being involved in neurocognitive impairment after posterior fossa tumor treatment in children. Author Affiliation: (1) Arbeitsbereich Padiatrische Neurochirurgie, Charite-Universitatsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany (2) Klinik fur Padiatrie mit Schwerpunkt Onkologie und Hamatologie, Berlin, Germany (3) Radiologie, Charite-Universitatsmedizin Berlin, Berlin, Germany (4) Neurochirurgische Klinik, Medizinischen Universitat Innsbruck, Innsbruck, Austria Article History: Registration Date: 14/11/2012 Received Date: 03/09/2012 Accepted Date: 13/11/2012 Online Date: 27/11/2012
    Keywords: Mutism -- Causes Of ; Mutism -- Diagnosis ; Mutism -- Care And Treatment ; Mutism -- Research ; Tumor Removal -- Complications And Side Effects ; Tumor Removal -- Research
    ISSN: 0256-7040
    Source: Cengage Learning, Inc.
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  • 6
    Language: English
    In: European Journal of Paediatric Neurology, January 2016, Vol.20(1), pp.25-37
    Description: 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 14.63 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. 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 (  = −0.39,  = 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.
    Keywords: Cerebellum ; Posterior Fossa Tumors ; Forward Thinking ; Processing Speed ; Working Memory ; Set Shifting ; Medicine
    ISSN: 1090-3798
    E-ISSN: 1532-2130
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  • 7
    Language: English
    In: Annals of Hematology, 2017, Vol.96(2), pp.199-213
    Description: Cerebrovascular disease is an important feature of pediatric sickle cell disease (SCD) and may lead to cognitive and motor impairment. Our cross-sectional study examined the incidence and severity of these impairments in a pediatric cohort without clinical cerebrovascular events from Berlin of mixed ethnic origin. Thirty-two SCD patients (mean age 11.14 years, range 7.0–17.25 years; males 14) were evaluated for full-scale intelligence (IQ) (German version WISC-III), fine motor function (digital writing tablet), and executive function (planning, attention, working memory, and visual-spatial abilities) with the Amsterdam Neuropsychological Tasks (ANT) program and the Tower of London (ToL). Data on clinical risk factors were retrieved from medical records. Full-scale IQ of patients was preserved, whereas performance IQ was significantly reduced (91.19 (SD 12.17) d  = 0.7, p  = 0.007). SCD patients scored significantly lower than healthy peers when tested for executive and fine motor functions, e.g., planning time in the ToL (6.73 s (SD 3.21) vs. 5.9 s in healthy peers (SD 2.33), d  = 0.5, p  = 〈0.001) and frequency on the writing tablet (mean z score −0.79, d  = 0.7, p  〈 0.001). No clinical risk factors were significantly associated with incidence and severity of cognitive and motor deficits. Despite the preservation of full-scale IQ, our SCD cohort of mixed origin exhibited inferior executive abilities and reduced fine motor skills. Our study is limited by the small size of our cohort as well as the lack for control of sociodemographic and socioeconomic factors modulating higher functions but highlights the need for early screening, prevention, and specific interventions for these deficits.
    Keywords: Children ; Sickle cell disease ; Fine motor function ; Intelligence ; Attention ; Cerebral infarcts/cerebrovascular disease
    ISSN: 0939-5555
    E-ISSN: 1432-0584
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  • 8
    Language: English
    In: Child's Nervous System, 2011, Vol.27(3), pp.407-413
    Description: Purpose Patients with medulloblastoma are exposed to ototoxic treatments including radiation therapy and platinum chemotherapy. The favorable toxicity profile of carboplatin led us to substitute this chemotherapeutic agent for cisplatin in the HIT-1991, HIT-MED-1999, and HIT-2000 chemotherapy protocols. We retrospectively investigated its consequences in terms of overall survival and ototoxicity rates. Methods Twenty-four medulloblastoma patients were treated according to HIT protocols with carboplatin substitution between April 1999 and June 2006. Nineteen (79%) patients had adequate baseline and post-treatment audiological data. Mean age at diagnosis was 9.3 (range 3.5-18.9) years with a mean follow-up time of 30.8 (8.1-111.3) months. Patients received a mean carboplatin cumulative dose of 2,131 (830-4312) mg/m². Results Twenty-three patients were alive at the time of assessment. Hearing loss greater than 20 dB was observed in two (10.5%) of 19 patients. Both had grade 2 ototoxicity according to Brock's scale. There were no significant differences between the patients' baseline and post-treatment audiograms at any frequency. The observed hearing loss was significantly correlated to younger age at diagnosis and cumulative carboplatin dose (p 〈 0.05). Conclusions The encouraging overall survival and low hearing loss rates in this medulloblastoma patient cohort suggest that protocols containing carboplatin may offer a viable alternative to standard cisplatin protocols and warrant further investigation. ; Includes references ; p. 407-413.
    Keywords: Carboplatin ; Platinum-induced ototoxicity ; Medulloblastoma ; Hearing loss ; Childhood brain cancer survivors
    ISSN: 0256-7040
    E-ISSN: 1433-0350
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  • 9
    Language: English
    In: PLoS ONE, 01 January 2013, Vol.8(11), p.e78599
    Description: OBJECTIVE: Using multidisciplinary treatment modalities the majority of children with cancer can be cured but we are increasingly faced with therapy-related toxicities. We studied brain morphology and neurocognitive functions in adolescent and young adult survivors of childhood acute, low and standard risk lymphoblastic leukemia (ALL), which was successfully treated with chemotherapy. We expected that intravenous and intrathecal chemotherapy administered in childhood will affect grey matter structures, including hippocampus and olfactory bulbs, areas where postnatal neurogenesis is ongoing. METHODS: We examined 27 ALL-survivors and 27 age-matched healthy controls, ages 15-22 years. ALL-survivors developed disease prior to their 11th birthday without central nervous system involvement, were treated with intrathecal and systemic chemotherapy and received no radiation. Volumes of grey, white matter and olfactory bulbs were measured on T1 and T2 magnetic resonance images manually, using FIRST (FMRIB's integrated Registration and Segmentation Tool) and voxel-based morphometry (VBM). Memory, executive functions, attention, intelligence and olfaction were assessed. RESULTS: Mean volumes of left hippocampus, amygdala, thalamus and nucleus accumbens were smaller in the ALL group. VBM analysis revealed significantly smaller volumes of the left calcarine gyrus, both lingual gyri and the left precuneus. DTI data analysis provided no evidence for white matter pathology. Lower scores in hippocampus-dependent memory were measured in ALL-subjects, while lower figural memory correlated with smaller hippocampal volumes. INTERPRETATION: Findings demonstrate that childhood ALL, treated with chemotherapy, is associated with smaller grey matter volumes of neocortical and subcortical grey matter and lower hippocampal memory performance in adolescence and adulthood.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 10
    Language: English
    In: Journal of Neuro-Oncology, 2010, Vol.100(2), pp.199-207
    Description: Pediatric neurofibromatosis type 1 (NF-1) patients are prone to developing low-grade glioma (LGG). The HIT-LGG study 1996 aimed to observe the natural history of pediatric LGG and to postpone irradiation in younger children by using carboplatinum and vincristine in case non-surgical treatment was required. A total of 109 of 1,044 (10.4%) protocol patients had a genetic NF-1 trait [57 female patients; median age 5.1 years (range 1–15.4 years)]. Eighty-three patients (76%) suffered from an optic pathway tumor. Neuroimaging only allowed diagnosis in 67 patients. Histology revealed pilocytic astrocytoma WHO grade I in 38 of 42 biopsied patients. Sixty-five (60%) patients received non-surgical treatment, either chemotherapy ( n  = 55) or irradiation ( n  = 10). The overall survival rate of 96% after a median observation time of 5.25 years contrasts with an event free survival rate (EFS) of 0.24 at 5 years. Progressive LGG were observed even in children older than 11 years. Chiasmatic/postchiasmatic localization was a univariate risk factor for progressive disease. In the chemotherapy group, we observed a 5-year progression-free survival (PFS) rate of 0.73. Similarly, the PFS rate in the irradiation group was 0.78. Multivariate analysis revealed surgical intervention and localization within the optic pathway as factors that increased the risk of tumor progression. In this large prospective multinational study, LGG in NF-1 patients did progress in 75% of patients. Chemotherapy yielded acceptable PFS. The biological factors determining progression remain poorly understood.
    Keywords: Low grade glioma ; Chemotherapy ; Radiotherapy ; NF-1 ; Children
    ISSN: 0167-594X
    E-ISSN: 1573-7373
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