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Recent research has shown that sex/gender (s/g) influences on cognitive functions and related brain anatomy, functional responses, and connectivity are less clear than previously assumed, and most studies investigated adult population. In this mini-review, we summarize research progress in the study of s/g differences in the human brain function as investigated by neuroimaging methods adopting a developmental perspective. In particular, we review original studies published from 2000 to 2021 investigating s/g differences in task-related brain functional activation and connectivity in healthy children and adolescents. We summarize results about studies in the domains of language, visuospatial ability, social cognition, and executive functions. Overall, a clear relation between cognition and brain activation or connectivity pattern is far from being established and the few coherent results should be considered exploratory, despite in some cases, brain function seems to present specific patterns in comparison with what reported in adults. Moreover, future studies should address methodological limitations, such as fragmentation of tasks, lack of control for confounding variables, and lack of longitudinal designs to study developmental trajectories.

Language processing depends on an integrated circuit involving the left supratentorial language areas and the right posterior lateral cerebellar hemisphere (lobule VI, lobule VII, Crus I, and Crus II). Reorganization of the language system after lesions of the cerebral language areas includes also cerebellar relocation. This is the first study assessing functional language reorganization after lesions concerning primarily the cerebellum, using a fMRI paradigm of phonological covert word production task in six children operated for right cerebellar astrocytoma and in 15 typically developing children. We found right cerebellar and left frontal activations in healthy controls and high variability of reorganizational patterns in patients with early right cerebellar lesion. Also lesions not located in the areas typically involved in language tasks (Crus I and Crus II) can cause reorganization between the two hemispheres or hemispheric language reinforcement of the original lateralization. We discuss the role of several variables in determining the reorganizational pattern such as the site, extension, and timing of surgery. No variables revealed as predictors, suggesting that co-occurring influence of other biological and/or pathological factors are not yet demonstrated. Lesions in the postero-lateral cerebellum seem related to less efficient language performances, as an indicator of the system's functioning.

Basal ganglia are subcortical structures specialized at very early age, functionally different according to the right or left side. They are part of complex distributed network composed by parallel segregated loops where specific information are processed and open loops where different information are integrated. These loops are connected to specialized cortical areas thus entering into distributed processing of higher order cognitive functions and behaviours. Lesion or malfunction of basal ganglia nuclei cause deficits in different neuropsychological functions and neurobehavioural diseases, such Autism Spectrum Disorder, Attention Deficit/Hyperactivity Disorder, Tourette syndrome, etc., for the reciprocal connections from and to the limbic system and the frontal system. Basal ganglia have a computational functioning, working by activation and inhibition sequences, coded in time and space and regulated by inhibitory and excitatory mechanisms, with such accuracy to guarantee an effective and elegant product.

Aim The purpose of the present study was to correlate early hand function assessment during the first years of life with neuroimaging findings and the different patterns of cortico-motor reorganization in children with unilateral cerebral palsy (UCP). Methods We conducted a long prospective observational study, in which 17 children with UCP (8 left-sided hemiplegia; Manual Ability Classification System level 1–3) were first assessed at a mean age of 24 months (range 18–28), and followed up by means of the Besta Scale, a new standardized protocol assessing both unimanual and bimanual hand function. They also underwent Melbourne Assessment of Unilateral Upper Limb Function (MUUL) and single-pulse Transcranial Magnetic Stimulation (TMS) at a mean age of 10 years 5 months (range 9 y 1 m–12 y 8 m). Brain MRIs of all the 17 children were independently assessed and scored by two blinded observers, according to a defined protocol. Possible correlations between hand function at first assessment, neuroimaging and TMS data were analyzed. Results Early hand function impairment significantly correlated with the extension of brain damage ( ρ = −0.531, p = 0.028), number of involved areas ( ρ = −0.608, p = 0.010), presence of radiological signs of cortico-spinal degeneration ( ρ = −0.628, p = 0.007), and basal ganglia involvement ( ρ = −0.485, p = 0.049). Additionally, higher hand function scores (i.e. better hand function) at first assessment significantly correlated with contralateral cortico-spinal projections, while lower scores significantly correlated with either mixed or ipsilateral cortico-spinal projections to the affected hand ( χ 2 (2) = 11.418, p = 0.003; post-hoc tests: contralateral TMS group versus ipsilateral: Z = −2.943, p = 0.002 and contralateral TMS group versus mixed: Z = −2.775, p = 0.006). Conclusions To our knowledge, this is the first study correlating hand function assessment in the first years of life, and its evolution over time, with neuroimaging and cortico-spinal projection patterns in children with UCP. These findings could contribute to an improved prediction of prognosis and a better delineation of therapeutic interventions in young children with UCP.

Genetic analysis of Neurofibromatosis type 1 (NF1) may facilitate the identification of patients in early phases of the disease. Here, we present an overview of our diagnostic research spanning the last 11 years, with a focus on the description of 225 NF1 mutations, 126 of which are novel, found in a series of 607 patients (513 unrelated) in Italy. Between 2003 and 2013, 443 unrelated patients were profiled by denaturing high pressure liquid chromatography (DHPLC) analysis of 60 amplicons derived from genomic NF1 DNA and subsequent sequencing of heterozygotic PCR products. In addition, a subset of patients was studied by multiplex ligation‐dependent probe amplification (MLPA) to identify any duplications, large deletions or microdeletions present at the locus. Over the last year, 70 unrelated patients were investigated by MLPA and sequencing of 22 amplicons spanning the entire NF1 cDNA. Mutations were found in 70% of the 293 patients studied by DHPLC, thereby fulfilling the NIH criterion for the clinical diagnosis of NF1 (detection rate: 70%); furthermore, 87% of the patients studied by RNA sequencing were genetically characterized. Mutations were also found in 36 of the 159 patients not fulfilling the NIH clinical criteria. We confirmed a higher incidence of intellectual disability in patients harboring microdeletion type 1 and observed a correlation between a mild phenotype and the small deletion c.2970_2972delAAT or the missense alteration in amino acid residue 1809 (p.Arg1809Cys). These data support the use of RNA‐based methods for genetic analysis and provide novel information for improving the management of symptoms in oligosymptomatic patients.

Electroencephalographic (EEG) photoparoxysmal response has been little investigated in very young patients. We studied 5055 patients aged less than 5 years with no acquired brain damage, who underwent EEG recording. We determined the prevalence and significance of photoparoxysmal response induced by 1 to 20 Hz photic stimulation. Fifty-three showed photoparoxysmal response and were diagnosed as having Dravet syndrome (11), epileptic encephalopathy with myoclonic seizures (8), neurodegenerative disorders (8), benign idiopathic epilepsies (9), and static disorders with a known or suspected genetic origin (17). Photoparoxysmal response occurred in response to 1 to 5 Hz trains in 41.5% subjects. In most patients with epileptic encephalopathies, photoparoxysmal response was a transient finding: in 53.2%, it failed to be replicated in the recordings performed more than 6 months after initial evaluation. Photoparoxysmal response is rare in patients aged less than 5 years and has some peculiarities such as occurrence with low-frequency stimuli. Its distribution in specific conditions indicates that photoparoxysmal response may be useful in diagnostic workup.

Voxel-based morphometry (VBM) studies have reported abnormalities in brain regions involved in functions that are commonly impaired in autism spectrum disorders (ASD). However, little is known about brain structure anomalies in low-functioning (LF) young children with ASD. A VBM analysis was carried out to assess brain regions involved in ASD LF children, and a multiple regression analysis was used to examine the relationship between regional volume changes and autism symptom measures. Twenty-six LF ASD children (2-10 years) were compared with 21 controls. A VBM-Diffeomorphic Anatomical Registration analysis using Exponentiated Lie algebra (DARTEL) was used to evaluate gray matter (GM) and white matter alterations, covaried with Intelligence Quotient, age, and total brain volume. The resulting altered regions were correlated with Autism Diagnostic Interview (ADI)-Revised and Autism Diagnostic Observation Schedule (ADOS)-Generic scores. GM bilateral reduction was noted in the cerebellum (Crus II and vermis) and in the hippocampi in ASD group. GM reduction was also detected in the inferior and superior frontal gyri, in the occipital medial and superior gyri, and in the inferior temporal gyrus of the left cerebral hemisphere. In the right hemisphere, GM reduction was found in the post-central cortex and in the occipital inferior gyrus. Multiple regression analysis showed a correlation between alterations in GM volume in the cerebellum (Crus II and vermis) and ADI-communication and ADOS-total (communication and interaction) scores. These findings seem to confirm that the cerebellum is involved in integrating and regulating emotional and cognitive functions which are impaired in ASD.

Background: Bilateral perisylvian polymicrogyria (BPP) is a well-recognized malformation of cortical development commonly associated with epilepsy, cognitive impairment, and oromotor apraxia. Reports have suggested the association of BPP with arthrogryposis multiplex congenita. We sought to investigate the clinical, electrophysiological, and neuroradiological features of this combined syndrome to determine if there are unique features that distinguish BPP with arthrogryposis from BPP alone. Methods: Cases of BPP with congenital arthrogryposis were identified from a large research database of individuals with polymicrogyria. Clinical features (including oromotor function, seizures, and joint contractures), MR brain imaging, and results of neuromuscular testing were reviewed. Results: Ten cases of BPP with congenital arthrogryposis were identified. Most cases had some degree of oromotor apraxia. Only a few had seizures, but a majority of cases were still young children. Electrophysiological studies provided evidence for lower motor neuron or peripheral nervous system involvement. On brain imaging, bilateral polymicrogyria (PMG) centered along the Sylvian fissures was seen, with variable extension frontally or parietally; no other cortical malformations were present. We did not identify obvious neuroimaging features that distinguish this syndrome from that of BPP without arthrogryposis. Conclusions: The clinical and neuroimaging features of the syndrome of BPP with congenital arthrogryposis appear similar to those seen in cases of isolated BPP without joint contractures, but electrophysiological studies often demonstrate coexistent lower motor neuron or peripheral nervous system pathology. These findings suggest that BPP with arthrogryposis may have a genetic etiology with effects at two levels of the neuraxis.

We present the neuropsychological and linguistic follow-up of a girl with bilateral perisylvian polymicrogyria during 4 years of gestural and verbal speech therapy. Some researchers have suggested that children with bilateral perisylvian polymicrogyria mentally fail to reach the syntactic phase and do not acquire a productive morphology. This patient achieved a mean length of utterance in signs/gestures of 3.4, a syntactic phase of completion of the nuclear sentence and the use of morphological modifications. We discuss the link between gesture and language and formulate hypotheses on the role of gestural input on the reorganization of compensatory synaptic circuits.

Human ciliopathies are hereditary conditions caused by defects of proteins expressed at the primary cilium. Among ciliopathies, Joubert syndrome and related disorders (JSRD), Meckel syndrome (MKS) and nephronophthisis (NPH) present clinical and genetic overlap, being allelic at several loci. One of the most interesting gene is TMEM67, encoding the transmembrane protein meckelin. We performed mutation analysis of TMEM67 in 341 probands, including 265 JSRD representative of all clinical subgroups and 76 MKS fetuses. We identified 33 distinct mutations, of which 20 were novel, in 8/10 (80%) JS with liver involvement (COACH phenotype) and 12/76 (16%) MKS fetuses. No mutations were found in other JSRD subtypes, confirming the strong association between TMEM67 mutations and liver involvement. Literature review of all published TMEM67 mutated cases was performed to delineate genotype-phenotype correlates. In particular, comparison of the types of mutations and their distribution along the gene in lethal versus non lethal phenotypes showed in MKS patients a significant enrichment of missense mutations falling in TMEM67 exons 8 to 15, especially when in combination with a truncating mutation. These exons encode for a region of unknown function in the extracellular domain of meckelin.

Purpose With a view to improving the prognosis for patients with metastatic medulloblastoma, we tested the efficacy and toxicity of a hyperfractionated accelerated radiotherapy (HART) regimen delivered after intensive sequential chemotherapy. Patients and Methods Between 1998 and 2007, 33 consecutive patients received postoperative methotrexate (8 g/m2), etoposide (2.4 g/m2), cyclophosphamide (4 g/m2), and carboplatin (0.8 g/m2) in a 2-month schedule, then HART with a maximal dose to the neuraxis of 39 Gy (1.3 Gy/fraction, 2 fractions/d) and a posterior fossa boost up to 60 Gy (1.5 Gy/fraction,2 fractions/d). Patients with persistent disseminated disease before HART were consolidated with two myeloablative courses and circulating progenitor cell rescue. Results Patients were classified as having M1 (n = 9), M2 (n = 6), M3 (n = 17), and M4 (n = 1) disease. Seven patients younger than 10 years old who achieved complete response after chemotherapy received a lower dose to the neuraxis (31.2 Gy). Twenty-two of the 32 assessable patients responded to chemotherapy; disease was stable in five patients and progressed in five patients. One septic death occurred before radiotherapy. Eight patients experienced relapse after a median of 12 months. Fourteen of the 33 patients underwent consolidation therapy after HART. With a median 82-month survivor follow-up, the 5-year event-free, progression-free, and overall survival rates were 70%, 72%, and 73%, respectively. No severe clinical complications of HART have emerged so far. Conclusion HART after intensive postoperative chemotherapy, followed by myeloablative chemotherapy in selected cases, proved feasible in children with metastatic medulloblastoma. The results of our treatment compare favorably with other series treated using conventional therapies.

The Judgment of Line Orientation test (JLO) is widely used to assess visuospatial processing. To investigate whether JLO is impaired compared to the normal population, whether it is worse if the lesion affects right-hemisphere or cerebral structures involved in JLO processing in adults, and how JLO correlates with the extent of the lesion, Wechsler Intelligence Scale for Children (WISC) IQs and WISC subtests, we assessed 20 children with congenital unilateral lesion (12 left and 8 right). Only 50% of our children had a borderline or significantly impaired performance in the JLO test, with a prevalence of females and left-hemisphere-impaired participants. The brain areas affected do not generally coincide with the network identified by functional magnetic resonance imaging (fMRI) on healthy adults, suggesting that the neural correlates are distributed differently in children depending on their age and on functional reorganization. Further research, including functional studies on larger samples of children of different age groups, are needed to elucidate the network subserving this ability in developmental age.

To underline the importance of Environmental Factors for reducing Disability and to demonstrate the complex condition of life, especially in terms of social inclusion and participation for children and adolescents affected by brain tumour.An observational study applying the ICF version for Children and Youth (ICF-CY), the quality of life KIDSCREEN questionnaires and the Vineland assessment was performed. Age-specific ICF-CY Questionnaires were used to interview children at three time-points.Twenty-nine children were enrolled. Social life and relationships were crucial for defining children's disability level: formal and informal relationships showed to be very relevant to improve functioning (presence of facilitators in terms of more that 20% of cases). The severity of the disease makes the attention deeply focussed on treatment, neglecting other very important aspects in children's or adolescents' life such as their participation in life.The project highlighted some relevant issues about functioning and disability of these patients, in light of ICF's Biopsychosocial model of disability. Different rehabilitation projects are necessary for children and adolescents living after brain tumour. Considering treatment and the severity of tumour is very important to define pathways that should also include social and interpersonal aspects.

Verbal learning and retrieval, as well as the use of learning strategies, were assessed in 24 children with benign epilepsy with centrotemporal spikes (BECTS) and 16 controls, using the California Verbal Learning Test-Children's Version. Neuropsychological data were correlated with EEG features. Compared with age-matched controls, the children with BECTS younger than 10 exhibited significant learning difficulties and were less efficient in using a semantic clustering strategy, whereas no such difference emerged for subjects older than 10. This suggests that the capacity for spontaneous use of a more efficient strategy matures later in children with BECTS. Moreover, the majority of those younger than 10 had multifocal anomalies, suggesting that the difficulties encountered might be caused by the presence of additional foci.

Aicardi-Goutières syndrome (AGS) is a genetically determined encephalopathy usually inherited as an autosomal recessive trait. The syndrome can be caused by mutations in the AGS1 gene encoding the exonuclease TREX1, or in any of the AGS2, AGS3, or AGS4 genes that encode the three subunits of the human ribonuclease H2 (RNaseH2) complex. Typically, AGS has an early onset, usually manifesting by the age of 4 months. We describe a female infant in whom the onset of the neurological symptoms of AGS occurred after the age of 12 months, and her younger brother who was identified to be affected by AGS at the age of 8 months on the basis of the presence of non-neurological features alone. This paper is important in providing a detailed description of the late-onset presentation of AGS in patients with proven pathogenic mutations and highlights the occurrence of both chilblains and abnormal neuroimaging many months before the onset of neurological features. Our paper also considers the possible value of immunomodulatory therapy in AGS.

Patients with diffuse pontine gliomas have a median survival of less than one year and represent a challenge for pediatric oncologists, prompting them to attempt experimental therapies. From 1987 to 2005, 62 children with diffuse pontine glioma, not amenable to curative surgery, were treated according to four successive pilot protocols: (1) concomitant chemo-radiotherapy (etoposide, cytarabine, ifosfamide, cisplatin, and dactinomycin); (2) intensive high-dose courses chemotherapy (cisplatin/etoposide, cyclophosphamide/vincristine/methotrexate) and a subsequent course of myeloablative thiotepa followed by radiation and maintenance chemotherapy; (3) cisplatin/etoposide followed by isotretinoin before, during and after focal irradiation; and (4) iv vinorelbine before, during, and after irradiation. Considering all patients, 77% experienced a transient response to treatment, always detectable after radiotherapy. The progression-free survival (PFS) rate was 25 +/- 6% at one year, median PFS was seven months; overall survival (OS) was 45 +/- 6%, median OS was eleven months: no statistical differences in the four studies in terms of outcome were detected. Despite improved diagnostic, therapeutic, and supportive tools in pediatric neuro-oncology, little has been achieved for patients with diffuse pontine tumors.

We assessed intelligence and receptive and expressive language skills in 6 children, ages 7 years 9 months to 12 years 4 months, with bilateral perisylvian polymicrogyria of variable extent and with dysarthria of different severity. In view of the recent findings of a close relationship between word and gesture, we also examined the communicative use of gesture. We found that mental retardation was related to the extent of cortical malformation; lexical comprehension, but not morphosyntactic comprehension, and verbal production were more compromised than expected from nonverbal intellectual abilities; lack of verbal language was not compensated by the use of referential gestures. Results are discussed suggesting that compromised verbal and gestural communication in bilateral perisylvian polymicrogyria are not due simply to mental retardation and/or dysarthria but also to dysfunction of Sylvian fissure areas concerned with the totality of language processing.

Although relations between the extent of periventricular leukomalacia and neuropsychological performance in preterm children with spastic diplegia have been extensively investigated, studies on term children with spastic diplegia are rare. The authors examined 15 preterm children and 9 term children with spastic diplegia, all of whom had periventricular leukomalacia as a main magnetic resonance imaging (MRI) finding (excluding full-term spastic diplegic children with other MRI findings). Cognitive abilities (Griffith scale) and visuoperceptual abilities (Developmental Test of Visual Perception) were compared in the 2 groups and related to periventricular leukomalacia severity. Cognitive performance was substantially similar in the 2 groups. However, the overall Developmental Test of Visual Perception scores were below normal in the preterm and were normal in the term children; furthermore, visuoperceptual abilities were differentially affected in the preterm children, with visuomotor abilities more compromised than nonmotor visuoperceptual abilities. These children had similar cognitive performance and MRI findings, so the greater visuoperceptual compromise in the preterm group suggests a direct influence of prematurity, which may have adversely influenced the reorganization of visual centers and pathways following the initial developmental insult. The strabismus present in most preterm children would also have contributed to their greater visuoperceptual compromise. The authors conclude that the management of preterm and term children should differ, with concentration on visuoperceptual skills and rehabilitation in the former.

Recent research has revealed that benign childhood epilepsy with centrotemporal spikes (BECTS) causes deficient performance in various neuropsychological areas, without arriving at a definition of a uniform profile. The purpose of this study was to examine intelligence and certain language functions in 24 children with an active centrotemporal focus, comparing them with a group of 16 controls matched for age and schooling. Test results were correlated with several EEG characteristics, including focal versus multifocal presentation of interictal epileptiform activity, lateralization, spike maximum on midtemporal or extratemporal electrodes, and rate of interictal activity when awake and during non-REM sleep. Our study demonstrated that children with BECTS have mild language defects, revealed by tests measuring phonemic fluency, verbal re-elaboration of semantic knowledge, and lexical comprehension. Interictal EEG discharges demonstrated that a high rate of occurrence while awake, multifocal location, and temporal prominence seem to impair the efficiency of some of the neuropsychological functions investigated. However, because the last EEG was obtained within the last 2 months (on average) before the assessment, and because BECTS is a form of epilepsy with signs of cortical hyperexcitability that vary over time in terms of rate, side, and location, the pattern of neuropsychological deficiencies could have changed (at least to some degree) by the time of the test, with respect to the EEG variables considered.

Inhibition problems are reportedly at the heart of several childhood pathologies and learning disorders, but few instruments are available for their in-depth investigation. The main aim of the present study was to investigate the development of a capacity to inhibit automatic responses in young and middle childhood. For this purpose, 100 children between 6 and 11 years old were administered two tests that measure executive inhibition: an animal Stroop task (in a paper-and-pencil version of the computerized original proposed by Wright and colleagues in 2003) and a conflicting motor response task. Our results indicate that performance clearly improves in both tests during the course of a child's development and the data obtained with the paper-and-pencil animal Stroop task overlap with those obtained with the computerized version. When the task calls for a stronger inhibitory control (the incongruent situation in the Stroop task and in the opposite condition in the conflicting motor response test) the trend of the response times is less homogeneous, peaking in the youngest and oldest age brackets considered. The positivity and significance of the correlation coefficients between the two tests also suggest that the two measures are tapping cognitive abilities that are developing in a parallel fashion.

Childhood malignant gliomas are rare, but their clinical behavior is almost as aggressive as in adults, with resistance to therapy, rapid progression, and not uncommonly, dissemination. Our study protocol incorporated sequential chemotherapy and high-dose thiotepa in the preradiant phase, followed by focal radiotherapy and maintenance with vincristine and lomustine for a total duration of one year. The induction treatment consisted of two courses of cisplatin (30 mg/m2) plus etoposide (150 mg/m2) × 3 days and of vincristine (1.4 mg/m2) plus cyclophosphamide (1.5 g/m2) plus high-dose methotrexate (8 g/m2), followed by high-dose thiotepa (300 mg/m2 × 3 doses), with harvesting of peripheral blood progenitor cells after the first cisplatin/etoposide course. From August 1996 to March 2003, 21 children, 14 females and 7 males, with a median age of 10 years were enrolled, 18 presenting with residual disease after surgery. Histologies were glioblastoma multiforme in 10, anaplastic astrocytoma in nine, and anaplastic oligodendroglioma in two; sites of origin were supratentorial areas in 17, spine in two, and posterior fossa in two. Of the 21 patients, 12 have died (10 after relapse, with a median time to progression for the whole series of 14 months; one with intratumoral bleeding at 40 months after diagnosis; and one affected by Turcot syndrome for duodenal cancer relapse). Four of 12 relapsed children had tumor dissemination. At a median follow-up of 57 months, overall survival and progression-free survival at four years were 43% and 46%, respectively. Sequential and high-dose chemotherapy can be afforded in front-line therapy of childhood malignant glioma without excessive morbidity and rather encouraging results.

Numerous studies on adults have confirmed that the cerebellum has a role in processing higher brain functions, and evidence of this role has emerged more recently in developmental age as well. Various types of congenital lesion are associated with neuropsychological impairments and behavioral changes that can sometimes even give rise to a picture of autism. Acquired cerebellar lesions (especially tumors and stroke) in children of normal intelligence have enabled different neuropsychological profiles to be identified, depending on the cerebellar site involved. In Chiari malformation, the cerebellar structures are squeezed and crowded inside the posterior fossa and along the time this could generate various kinds of cognitive and behavioral disorders. Currently available data remain inconclusive, however, and prospective longitudinal studies on sizable series will be needed to ascertain whether and to what degree Chiari malformations may negatively affect mental functioning in developmental age.

This study presents developmental data for verbal and spatial memory tasks: Corsi's block-tapping test and Luria's verbal learning test. Norms have been collected from 275 primary and early secondary school children aged from 5 years, 4 months to 13 years, 6 months. Our results confirm a slow and constant improvement in performances over time, and the advantage of about 1.5 items of the verbal span over the spatial span supports the existence of developmental differences between separate memory systems. No significant sex difference was found even if a slight trend in verbal span favouring female subjects is present.

Increasing survival rates in malignant brain tumors treatment have directed attention to the side effects of long-term disease control. Nevertheless, although the treatment protocols are continuously remodelled, the quality of life of children surviving for a long time is still poor. The most severe sequelae are neurocognitive disorders, which are associated with neurobehavioural alterations. The last are partly derived directly from the lesion localisation and treatments, but are often reinforced by academic and social failure. The deleterious effect of radiotherapy (CRT) is very well documented and confirmed in all the studies. The radiation dose delivered according to the age has reduced, but not fully eliminated, the negative influence on mental functioning. Also the CRT hyperfractionation has reduced, but not cancelled, this cognitive negative impact. Intrathecal methotrexate per se is responsible for a severe cognitive impairment, which can be even more severe in association to CRT. Some surgical approaches have been responsible for postoperative behavioural disturbances. Serial neuropsychological and behavioural evaluations, which should also include the survivors' own perception of their quality of life, are badly needed. The results of these evaluations should be covariate with several factors (age, type of surgery, lesion site, hydrocephalus, complementary therapies) in an attempt to define interdisciplinary treatment protocols to maximise survival while minimising cognitive/behavioural deficits.

We present data on the intellectual, language and executive functions of 26 children who had undergone surgery for the removal of cerebellar hemisphere or vermal tumours. The children with right cerebellar tumours presented with disturbances of auditory sequential memory and language processing, whereas those with left cerebellar tumours showed deficits on tests of spatial and visual sequential memory. The vermal lesions led to two profiles: (i) post-surgical mutism, which evolved into speech disorders or language disturbances similar to agrammatism; and (ii) behavioural disturbances ranging from irritability to behaviours reminiscent of autism. These data are consistent with the recently acknowledged role of the cerebellum as a modulator of mental and social functions, and suggest that this role is operative early in childhood.

To reduce the sequelae from CNS irradiation (RT), 16 children younger than 3 years with medulloblastoma-PNET (13 cases) and ependymoma (3 cases) were treated between 1987-1993 according to different postsurgical chemotherapy (CT) programs. None of these patients presented with metastases. Eleven patients were rendered disease-free by surgery, while 5 had residual tumor. Adjuvant therapy depended on patients' age, postsurgical status and parents' consent to radiotherapy (RT). Nine of the 16 infants remained alive in continuous complete remission from the first neoplasm (median follow-up 7 years). Three of them had been treated with CT alone and 6 with combined CT + RT (posterior fossa 4, whole CNS 2). Seven patients relapsed a median of 13 months after diagnosis, and all 7 of them died of their disease. Despite the omission of RT in 6 of the 16 patients and administration of only focal RT in 8 of the 16, the outcome of this series was satisfactory. Local failure (in 5/7 patients) was the major problem, despite the high dose of RT used in 2 of these 5. In 4 of 6 evaluable children school performance was satisfactory. One child in whom the entire CNS was irradiated developed glioblastoma multiforme 120 months after the first diagnosis of medulloblastoma.

Neurocognitive performance was evaluated in seven children with symptomatic partial epilepsy prior to, and at least 12 months after, discontinuation of carbamazepine. The patients treated with carbamazepine monotherapy were seizure-free for at least 2 years and without electroencephalographic anomalies for at least 1 year. Results indicated that carbamazepine at therapeutic levels does not affect intellectual, memory, or attentional functions, or more complex frontal functions. Nevertheless, after therapy withdrawal scores on frontal function tests used in this study improved significantly. This suggests that these functions could have been better without carbamazepine therapy. The fact that carbamazepine decreases neuron membrane excitability and could reduce the information circuity, particularly in the frontal areas, is offered as a possible explanation. Further studies on larger samples using the same design are required to validate these results. (J Child Neurol 1999; 14:357-362).

Late outcome in 12 children treated by radical surgery for craniopharyngioma is presented. None of the patients presented underwent fractionated traditional or stereotactic radiotherapy. The results show no neurological (except visual dysfunction in 6 subjects), cognitive or short-term memory deficits. Three children were found to have a minor attention deficit. In 5 cases "frontal lobe" malfunctioning was disclosed, and in 5 there were bursts of unpredictable anger. Three children showed worsening of functioning at school: a combination of various causes is suggested to explain the worsening of academic performances. The size of the sample calls for a careful evaluation of results, with due consideration for the influence of various factors on outcome. Multicentre studies are required to increase the sample size and achieve more general conclusions.

Rett syndrome and Angelman syndrome are two neurodevelopmental disorders characterized by partial overlapping features. Rett syndrome is frequently caused by a mutation in methyl-CpG-binding protein (MECP2) gene, localized on chromosome Xq28, whereas Angelman syndrome is frequently caused by different genetic anomalies at chromosome 15q11-q13 (deletions, uniparental disomy, imprinting center mutations, ubiquitin E3 ligase [UBE3A] gene mutations). Recently, some patients with a clinical diagnosis of Angelman syndrome were found to have a mutation in MECP2 gene. This report describes another patient with an Angelman-like phenotype and with an MECP2 mutation.

Progressive encephalopathy with edema, hypsarrhythmia, and optic nerve atrophy (PEHO) syndrome is a rare, apparently autosomal recessive condition in which characteristic dysmorphic features are associated with subcutaneous edema, visual deficit, early arrest of psychomotor development, seizures, and cerebellar atrophy. A condition similar to PEHO syndrome, but without the neuroradiologic or ophthalmologic signs, is known as PEHO-like syndrome. We present the case of a child with PEHO-like syndrome and underline the need for a careful follow-up of these patients to identify signs and symptoms that can have a later onset, such as optic atrophy. ( J Child Neurol 2005;20:454—456.)

8 long-surviving children, treated for medulloblastoma with combination radiotherapy and chemotherapy after surgery were examined in order to assess general intelligence, immediate attention and prolonged attention. Their siblings or first cousins were selected as controls. The children with medulloblastoma performed significantly worse than their peers, both in intelligence tests and attention tests. A trend towards a positive correlation between age at the start of treatment and IQs was confirmed in our study, while there was no evidence of a correlation between IQs and time elapsed from therapy. The role of chemotherapy, radiotherapy and their combination effect in producing neuropsychological sequelae is discussed.

We report the case of a child affected by a duplication of chromosome 13(q32-q34). This cytogenetic abnormality is rarely described in the literature. The description of our patient's characteristics might contribute to a better phenotype definition.

Neuropsychological impairment after removal of posterior fossa tumors is a recurrent issue in child neuropsychology and neurosurgery. The aim of this study was to assess verbal and performance intelligence, as well as immediate and sustained attention, in children with medulloblastoma or astrocytoma operated on for total removal of the lesion. Surgical treatment of medulloblastoma was always followed by chemoradiotherapy. Siblings of both tumor groups (without a history of neurological disease, even suspected) were examined as controls. The results were as follows: the cognitive performances were significantly poorer than the controls in both groups; the children with medulloblastoma scored below normal. Attention deficits were present in both groups as well when the usual clinical tests were used. When assessed by means of computerized methodology, the same function was normal. Considering that both groups of children underwent the same surgical treatment and all had hydrocephalus, the severe intellectual impairment reported only in patients with medulloblastoma can be ascribed to chemoradiotherapy. In contrast, the attention deficits present in both groups could be ascribed to the proximity of lesions to the ascending activating system. Malfunctioning of the activating system seems to be bypassed by the computerized administration of stimuli, which supplies motivation and kindles attention.