Virginie Kieffer

Injuries to Inferior Vermis and Dentate Nuclei Predict Poor Neurological and Neuropsychological Outcome in Children With Malignant Posterior Fossa Tumors

Children treated for a malignant posterior fossa tumor (PFT) are at risk of intellectual impairment. Its severity is not explained by age and radiotherapy alone. The current study was designed to define the correlations between the anatomical damage and the neurological/neuropsychological deficits in children with a malignant PFT.

Isolated corpus callosum agenesis: a ten‐year follow‐up after prenatal diagnosis (How are the children without corpus callosum at 10 years of age?)

Corpus callosum agenesis (CCA) is generally diagnosed in utero. Outcome appears to be better if the malformation is isolated. The aim of this study, which is the first one with a long (10 years) and standardized follow up, was to report cognitive abilities of children with isolated CCA diagnosed prenatally.

Cognitive and academic outcome after benign or malignant cerebellar tumor in children.

ObjectiveTo examine the impact of malignancy and location of the cerebellar tumor on motor, cognitive, and psychologic outcome. BackgroundAlthough many studies focus on long-term outcome after cerebellar tumor treatment in childhood, the impact of its precise location remains unclear. Patients and MethodsChildren, aged from 6 to 13 years, with a cerebellar malignant tumor (MT; MT group, n=20) or a cerebellar benign tumor (BT; BT group, n=19) were examined at least 6 months after the end of treatment using the international cooperative ataxia rating scale, the Purdue pegboard for manual skill assessment and the age-adapted Weschler scale. Structural changes in brain anatomy were evaluated and parents and teachers answered 2 independent questionnaires. ResultsParents and teachers reported high rate of learning and academic difficulties, but without any difference with respect to the type of tumor. However, children with cerebellar MT showed increased cognitive and motor difficulties compared with children with cerebellar BT. Cerebellar signs at clinical examination and manual skill impairment were strongly associated with cognitive difficulties. Both motor and cognitive impairments were found to be associated with extension of the lesion to the dentate nuclei. ConclusionsDentate nuclei lesions are major risk factors of motor and cognitive impairments in both cerebellar BT and MT.

Remediation of learning difficulties in children after treatment for a cerebellar medulloblastoma: A single-case study

In the process of establishing a methodology for individualized remediation programmes in children treated for cerebellar tumour, this study followed prospectively over 11 years a young child treated for a medulloblastoma at 18 months of age throughout the rehabilitation process. Repeated neuropsychological and academic evaluations evidenced temporary disruptive behaviour, deficient manual and visual abilities, attention and working memory difficulties, but preserved language abilities, in relation with vermian and left cerebellar damage. However, the described remediation programmes and interventions allowed the child to have fluent progression in school. Limits and benefits of rehabilitation are discussed. Con el propósito de establecer una metodología para los programas de remedio individualizados en niños tratados por tumores cerebelares, se estudiaron en forma prospectiva durante 11 años a niños de 18 meses de edad tratados por un meduloblastoma, a lo largo del proceso de rehabiitación. En relación al daño cerebelar y vermiano se pusieron en evidencia, a través de evaluaciones académicas y neuropsicológicas aplicadas en forma repetida, una conducta alterada en forma temporal, una deficiencia en las habilidades visuales y manuales, y la presencia de dificultades en la atención y en la memoria de trabajo, pero sin alteraciones en el lenguaje. Sin embargo, los programas de remedio y las intervenciones descritos le permitieron al niño tener una progreso correcto en la escuela. Se discuten los beneficios y los límites de la rehabilitación. Palabras clave: Cerebelo, meduloblastoma, remedio, resultado, rehabilitación en equipo

Tandem high-dose chemotherapy and autologous stem cell rescue in children with newly diagnosed high-risk medulloblastoma or supratentorial primitive neuro-ectodermic tumors

To assess the feasibility and effectiveness of high‐dose chemotherapy (HDC) with stem cell support followed by conventional craniospinal radiotherapy (RT) as treatment for children older than 5 years of age with newly diagnosed high‐risk medulloblastoma (MB) or supratentorial PNET (sPNET).

Inherited microdeletion in Xp21.3–22.1 involved in non-specific mental retardation

X‐linked mental retardation (XLMR) is a genetically and clinically neterogenous common disorder. A cumulative frequency of about 1/600 male births was estimated by different authors, including the fragile X syndrome, which affects 1/4000 males. Given this very high cumulative frequency, identification of genes and molecular mechanisms involved in other XLMRs, represents a challenging task of considerable medical importance. In this report we describe clinical and molecular investigations in the family of a mentally retarded boy for whom a microdeletion in Xp21.3–22.1 was detected within the frame of a previously reported systematic search for deletion using STS‐PCR screening. Thorough clinical investigation of the sibling showed that two affected brothers exhibit a moderate non‐specific mental retardation without any additional neurological impairment, statural growth deficiency or characteristic dysmorphy. Molecular analysis revealed that the microdeletion observed in this family is an inherited defect which cosegregates with mental retardation as an X‐linked recessive condition, since both non‐deleted boys and transmitting mother are normal. These results and the inherited microdeletion detected within the same region associated with non‐specific MR, reported by Raeymaekers et al., suggest that Xp21.3 MR locus is prone to deletions. Therefore, search for microdeletions in the eight families assigned by linkage analysis to this region might allow a better definition of the critical region and an identification of the gene involved in this X‐linked mental retardation.

Time perception in children treated for a cerebellar medulloblastoma.

The aim of the present study was to investigate temporal abilities in children treated by surgery for a malignant tumor in the cerebellum. Children with a diagnosed medulloblastoma and age-paired control children were given a temporal discrimination task (bisection task) and a temporal reproduction task with two duration ranges, one shorter than 1s and the other longer than 4s. The motor and cognitive capacities of these children were also assessed by a battery of age-adapted neuropsychological tests. The results did not show any significant difference in performance between the children with or without cerebellar lesions in the temporal discrimination task. It was only in the temporal reproduction task that the children with cerebellar lesions reproduced longer and more variable durations than the other children, but only for the short stimulus durations (≤ 1 s). In addition, a hierarchical regression analysis revealed that the best predictor of variance in temporal performance was a significantly lower processing speed in children with cerebellar lesions in comparison to their controls. These results indicated that the major cause of deficits in temporal judgments in children with cerebellar lesions was due to their inability to reproduce accurately short temporal intervals in association with low processing speed, rather than to a specific deficit in the perception of time.

Pseudoprogression after high-dose busulfan-thiotepa with autologous stem cell transplantation and radiation therapy in children with brain tumors: Impact on survival.

Children with a brain tumor treated with high-dose busulfan-thiotepa with autologous stem cell transplantation (ASCT) and radiation therapy (RT) often experience radiographic changes during follow-up. The purpose of the study was to identify the incidence, time course, risk factors, and clinical outcome of this complication. From May 1988 through May 2007, 110 patients (median age, 3.6 years; range, 1 month to 15.3 years) with a brain tumor had received 1 course of high-dose busulfan-thiotepa with stem cell rescue, followed or preceded by RT as part of their treatment. All MRI follow-up examinations were systematically reviewed. Twenty-three patients (21%) developed neuroradiological abnormalities at a median time of 9.2 months (range, 5.6-17.3 months) after ASCT. All contrast-enhancing lesions appeared in patients who had received RT after ASCT and were localized inside the 50-55Gy isodoses. They disappeared in 14 of 23 patients after a median time of 8 months (range, 3-17 months), leaving microcalcifications in some cases. The presence of MRI abnormalities was an independent prognostic factor for overall survival in the multivariate analysis (hazard ratio, 0.12; 95% confidence interval [CI], 0.04-0.33), with a 5-year overall survival rate of 84% among patients with MRI abnormalities (95% CI, 62-94), compared with 27% (95% CI, 19-37) among those without lesions. MRI-detectable pseudoprogression is a common early finding in children treated with high-dose busulfan-thiotepa followed by radiation therapy and is correlated with a better outcome.

Teachers’ report of learning and behavioural difficulties in children treated for cerebellar tumours

Primary objective: The aim of the study was the validation of the Deasy-Spinetta Questionnaire (DSQ) in 6–11 year olds with attention to the verification of three factors (learning difficulties, socialization and emotionality) and its application in children treated for cerebellar tumour. Methods and procedures: Twenty-nine children aged between 6–11 years were compared with 609 classmates. Teachers completed the DSQ. Patients were evaluated according to Wechsler Scales, the Purdue Pegboard and the International Cooperative Ataxia Rating scale. Main outcomes and results: In classmates, the DSQ factorial analysis showed three factors: learning, socialization difficulties and disturbing behaviour. Teachers reported more learning difficulties in patients than in classmates. Learning difficulties in patients were greater for mathematics and reasoning than for reading. Patients were described as less active, without evidence of autistic-like behaviour or irritability. The teachers’ report of learning difficulties was significantly correlated with IQ scores, but not with neurological deficits. Conclusions: The proposed DSQ scores are interesting for the assessment of learning and behavioural difficulties in children treated for cerebellar tumours, as they provide complementary ecological information to that given by clinical and neuropsychological testing.

Relapses of Optic Pathway Tumors After First-Line Chemotherapy

Chemotherapy is accepted as first‐line conservative treatment of optic pathway tumors in patients younger than 5. Limited data are available on the outcome of patients with recurrence/progression after initial chemotherapy.