Recommendations for the surveillance of mental health problems in childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Survivors of childhood, adolescent, and young adult (diagnosed when <25 years of age) cancer are at risk of mental health problems. The aim of this clinical practice guideline is to harmonise international recommendations for mental health surveillance in survivors of childhood, adolescent, and young adult cancer. This guideline was developed by a multidisciplinary panel of experts under the sponsorship of the International Guideline Harmonization Group.

Methylene tetrahydrofolate reductase A1298C polymorphisms influence the adult sequelae of chemotherapy in childhood-leukemia survivors.

This retrospective correlation study investigated the putative link between methylene tetrahydrofolate reductase (MTHFR) A1298C mutations and chemotherapy-related brain function changes in adult childhood-leukemia survivors. To this end, we determined the relationship between the particular MTHFR1298 genotype (AA, AC or CC) of 31 adult childhood-leukemia survivors, and (1) their CSF Tau and phosphorylated Tau (pTau) levels at the time of treatment, (2) their adult performance intelligence quotient (PIQ), and (3) their regional brain connectivity using diffusion magnetic resonance imaging (dMRI) and resting-state functional MRI (rsfMRI). We confirmed that neuropathology markers Tau and pTau significantly increased in CSF of children after intrathecal methotrexate administration.

Long-term leukoencephalopathy and neurocognitive functioning in childhood sarcoma patients treated with high-dose intravenous chemotherapy.

Purpose: Knowledge is limited regarding the prevalence and persistence of chemotherapy-induced leukoencephalopathy in childhood sarcoma patients. This study explored the presence, clinical relevance, and potential risk factors of leukoencephalopathy in childhood bone and soft tissue sarcoma survivors, treated with intravenous chemotherapy.

Methods: We acquired cross-sectional neurocognitive data in adult survivors (n = 34) (median age at diagnosis [AaD] = 13.

Methotrexate Affects Cerebrospinal Fluid Folate and Tau Levels and Induces Late Cognitive Deficits in Mice.

Intravenous and/or intrathecal administration of the anti-folate drug methotrexate is a common chemotherapeutic procedure in childhood leukemia. Therapeutic and prophylactic efficacy of these procedures notwithstanding, the occurrence of late adverse effects remains a cause of clinical concern in leukemia survivors. We propose an experimental mouse model to mimic the impact of methotrexate exposure on brain biochemistry and cell proliferation, as well as behavioral and neurocognitive functioning at adult age.

Neurocognitive Sequelae in Adult Childhood Leukemia Survivors Related to Levels of Phosphorylated Tau.

Central nervous system-directed prophylactic chemotherapy increases survival in childhood leukemia, but possible late neurocognitive sequelae remain a concern. We compared intellectual performance (WAIS IV), memory (AVLT), and executive functioning (ANT) between adult leukemia survivors (n = 31) and control individuals (n = 35). In survivors, cerebrospinal fluid (CSF) levels of phosphorylated Tau (p-Tau) during treatment and total intrathecal methotrexate dose correlated with adult intellectual performance (Pearson's and Spearman's coefficients, respectively).

Brain Connectivity and Cognitive Flexibility in Nonirradiated Adult Survivors of Childhood Leukemia.

Background: This study aimed to assess functional and structural brain connectivity in adult childhood leukemia survivors and the link with cognitive functioning and previously identified risk factors such as intrathecal methotrexate dose and age at start of therapy.

Methods: Thirty-one nonirradiated adult childhood leukemia survivors and 35 controls underwent cognitive testing and multimodal magnetic resonance imaging (resting state functional MRI, T1-weighted, diffusion-weighted, and myelin water imaging [MWI]). Analyses included dual regression, voxel-based morphometry, advanced diffusion, and MWI modeling techniques besides stepwise discriminant function analysis to identify the most affected executive cognitive domain.

Ring chromosome 20 syndrome: electroclinical description of six patients and review of the literature.

Background: Ring chromosome 20 syndrome is a rare chromosomal disorder.

Methods: In six patients, we focused on the presenting epileptic phenotype, the behavioral and mental problems and the relationship between the ratio of mosaicism and the age at onset of the epilepsy.

Results: All patients presented with pharmacoresistant frontal lobe complex partial seizures.

G37R SOD1 mutant alters mitochondrial complex I activity, Ca(2+) uptake and ATP production.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by selective death of motor neurons. Mutations in Cu/Zn superoxide dismutase-1 (SOD1) cause familial ALS but the molecular mechanisms whereby these mutations induce motor neuron death remain controversial. Here, we show that stable overexpression of mutant human SOD1 (G37R) - but not wild-type SOD1 (wt-SOD1) - in mouse neuroblastoma cells (N2a) results in morphological abnormalities of mitochondria accompanied by several dysfunctions.